Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) translocation, which juxtaposes the CCND1 (cyclin D1) gene with the immunoglobulin heavy chain enhancer, leading to constitutive cyclin D1 overexpression. MCL typically presents at advanced stage with lymphadenopathy, bone marrow involvement, and frequently gastrointestinal tract infiltration. While historically considered incurable with median survival of 3-5 years, outcomes have improved with BTK inhibitors (ibrutinib, acalabrutinib), high-dose therapy with stem cell transplant in younger patients, and emerging therapies including CAR-T cells.
Conditions with similar clinical presentations that must be differentiated from Mantle Cell Lymphoma:
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.
Please provide a comprehensive research report on Mantle Cell Lymphoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.
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This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details
Mantle cell lymphoma is a rare mature B-cell neoplasm arising from the mantle zone of lymphoid follicles (harmanen2024mantlecelllymphoma pages 31-34). Contemporary sources emphasize a wide clinical spectrum from indolent to aggressive behavior (lopez2024biologicalandclinical pages 1-2).
Direct abstract quote (2024, Blood Advances): “Mantle cell lymphoma (MCL) is an uncommon mature B-cell lymphoma that presents a clinical spectrum ranging from indolent to aggressive disease…” (López et al., Blood Advances, 2024-07; https://doi.org/10.1182/bloodadvances.2023011763) (lopez2024biologicalandclinical pages 1-2).
A 2024 registry thesis/review explicitly references the WHO 5th edition (2022) classification framework for haematolymphoid tumors and describes WHO-based categorization of MCL subtypes (harmanen2024mantlecelllymphoma pages 24-31, harmanen2024mantlecelllymphoma pages 31-34). A 2025 review also notes and cites both ICC (Blood 2022) and WHO 5th edition classification documents as key taxonomy references for MCL (ip2025updatesonthe pages 20-21).
MCL pathogenesis is strongly associated with a primary chromosomal translocation t(11;14)(q13;q32) that juxtaposes IGH::CCND1 and drives cyclin D1 overexpression (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 31-34). This event is commonly treated as the pathognomonic initiating lesion in disease-level reviews (lopez2024biologicalandclinical pages 1-2).
MCL is described as having significant genomic instability, affecting multiple processes including cell cycle regulation, cell survival, DNA damage response, telomere maintenance, NOTCH signaling, NF-κB/B-cell receptor (BCR) pathways, and chromatin modification (lopez2024biologicalandclinical pages 1-2).
Demographic risk factors: - Older age (typical onset >60 years; median age around mid-to-late 60s in multiple sources) and male predominance (male:female >2:1 reported in a 2024 registry source) (harmanen2024mantlecelllymphoma pages 31-34, lopez2024biologicalandclinical pages 1-2).
Molecular risk factors for aggressive disease / treatment resistance: - High tumor proliferation, blastoid morphology, TP53 alterations and/or CDKN2A/B inactivation, and high genetic complexity are repeatedly highlighted as adverse determinants of outcome with standard regimens (lopez2024biologicalandclinical pages 1-2).
No specific protective variants, lifestyle protective factors, or gene–environment interaction findings were identified in the retrieved 2023–2024 sources; therefore none are asserted here.
(Phenotype frequencies are not uniformly available across sources; terms below reflect typical clinical descriptors.) - Lymphadenopathy — HP:0002716 - Splenomegaly — HP:0001744 - Fever — HP:0001945 - Night sweats — HP:0030166 - Weight loss — HP:0001824 - Lymphocytosis — HP:0001974 (for leukemic presentations) - Anemia — HP:0001903 - Thrombocytopenia — HP:0001873
A 2024 registry source notes survivorship burdens and reports PTSD prevalence in survivors ≈3× higher than the general population (without providing detailed QoL instrument values in the excerpt) (harmanen2024mantlecelllymphoma pages 60-66). Disease- and treatment-related toxicity (e.g., cytopenias/infections with intensive therapy; CRS/ICANS with CAR-T) also plausibly impacts functioning, but detailed instrument-based QoL statistics were not captured in the retrieved excerpts.
Recent reviews/registry sources list frequent alterations including ATM, TP53, CDKN2A/B, and additional pathway-level changes (NOTCH; NF-κB/BCR; chromatin modifiers) (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 34-39).
A 2023 review provides example frequencies: CDKN2A deletions “Seen in 25% of MCL cases,” TP53 mutations ~11%, and 17p deletions up to 16% (md2023currenttreatmentsin pages 12-13).
Two major subtypes are emphasized: - Conventional MCL (cMCL): typically SOX11+, more genomically complex/aggressive (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 31-34). - Leukemic non-nodal MCL (nnMCL/LNN): ~10–20%, often SOX11−, more indolent with greater genomic stability; some initially asymptomatic/stable cases may progress over time (lopez2024biologicalandclinical pages 1-2, cencini2024survivaloutcomesof pages 1-2).
The retrieved sources did not provide specific, well-supported environmental, occupational, lifestyle, or infectious causal contributors unique to MCL. Therefore, no disease-specific environmental etiologies are asserted here.
A 2024 immunology review highlights macrophage contributions to prognosis and therapy response.
Direct abstract quote (2024, Frontiers in Immunology): “In Mantle Cell Lymphoma (MCL), the role of macrophages within the tumour microenvironment (TME) has recently gained attention due to their impact on prognosis and response to therapy.” (Nylund et al., Front Immunol, 2024-03; https://doi.org/10.3389/fimmu.2024.1373269) (nylund2024empoweringmacrophagesthe pages 1-2).
Mechanistic themes include: - M2-like macrophages (e.g., CD163+) linked to angiogenesis and immunosuppression (nylund2024empoweringmacrophagesthe pages 1-2). - Immunomodulation approaches: lenalidomide-associated reductions in CD163+ macrophages and enhanced phagocytosis; CD47-blockade + rituximab to increase phagocytosis (nylund2024empoweringmacrophagesthe pages 1-2).
Key diagnostic elements across sources include: - Histopathology on tissue biopsy (md2023currenttreatmentsin pages 12-13). - Immunophenotype typically includes B-cell markers (CD19, CD20) with cyclin D1 nuclear expression; MCL is often CD5+ (md2023currenttreatmentsin pages 12-13, harmanen2024mantlecelllymphoma pages 34-39). - FISH for IGH::CCND1 (t(11;14)) is emphasized as a preferred diagnostic method (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 34-39). - SOX11 immunohistochemistry as a diagnostic/subtyping tool, including cyclin D1-negative cases (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 31-34).
Frontline management remains risk- and fitness-adapted: - Younger/fit: cytarabine-containing regimens ± ASCT and rituximab maintenance (as summarized in 2024 real-world study) (cencini2024survivaloutcomesof pages 1-2). - Older/transplant-ineligible: bendamustine-rituximab (BR), R-BAC, VR-CAP (cencini2024survivaloutcomesof pages 1-2).
Relapsed/refractory MCL: BTK inhibitors are established therapies and CAR-T is implemented for appropriate patients.
Direct abstract quote (ZUMA-2 3-year follow-up, JCO 2023): “After a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91%… with 68% complete responses… medians for duration of response, progression-free survival, and overall survival were 28.2 months…, 25.8 months…, and 46.6 months…” (Wang et al., J Clin Oncol, 2023-01; https://doi.org/10.1200/JCO.21.02370) (wang2023threeyearfollowupof pages 1-2).
| Setting | Intervention | Study type/source | Key efficacy results (ORR/CR/PFS/OS with timepoints) | Safety notes (brief) | Publication date | URL | Evidence citation id(s) |
|---|---|---|---|---|---|---|---|
| R/R MCL | Brexucabtagene autoleucel (KTE-X19, anti-CD19 CAR-T) | Phase 2 pivotal follow-up, ZUMA-2; Wang et al., J Clin Oncol | Median follow-up 35.6 months; ORR 91%; CR 68%; median DOR 28.2 months; median PFS 25.8 months; median OS 46.6 months; 37% remained in ongoing response; month-6 MRD-negative patients (79% of assessable) had ORR 100% and DOR/PFS/OS not reached (wang2023threeyearfollowupof pages 9-10, wang2023threeyearfollowupof pages 1-2, wang2023threeyearfollowupof pages 3-4) | Late-onset toxicities infrequent; only 3% of treatment-emergent adverse events of interest occurred during extended follow-up; no new major CRS signal reported (wang2023threeyearfollowupof pages 9-10, wang2023threeyearfollowupof pages 1-2, wang2023threeyearfollowupof pages 3-4) | Jan 2023 | https://doi.org/10.1200/jco.21.02370 | (wang2023threeyearfollowupof pages 9-10, wang2023threeyearfollowupof pages 1-2, wang2023threeyearfollowupof pages 3-4) |
| R/R MCL | Brexucabtagene autoleucel (real-world) | Real-world leukapheresis/treated cohort summarized in Cencini 2024 | ORR 90%; CR 82%; estimated 12-month PFS 59%; median follow-up 14.3 months in cited real-life series (cencini2024survivaloutcomesof pages 2-3) | Feasibility limited by CRS, ICANS, prolonged cytopenia, and infections in real-world practice (cencini2024survivaloutcomesof pages 2-3) | Jan 2024 | https://doi.org/10.3390/hematolrep16010006 | (cencini2024survivaloutcomesof pages 2-3) |
| R/R MCL | Ibrutinib (covalent BTK inhibitor) | Real-world/literature summary in Cencini 2024 | Median PFS about 12.8 months overall; if used second line, PFS 25.4 vs 10.3 months and OS not reached vs 22.5 months compared with later-line use; after ibrutinib failure, median OS 2.9 months in a 114-patient retrospective series (cencini2024survivaloutcomesof pages 9-10, cencini2024survivaloutcomesof pages 1-2) | Outcomes particularly poor after BTKi failure; high-risk biology such as TP53 mutation associated with worse outcomes in summarized literature (cencini2024survivaloutcomesof pages 1-2) | Jan 2024 | https://doi.org/10.3390/hematolrep16010006 | (cencini2024survivaloutcomesof pages 9-10, cencini2024survivaloutcomesof pages 1-2) |
| Frontline / mixed real-world cohort | Contemporary real-life management era effect | Monocenter 73-patient retrospective cohort; Cencini et al., Hematology Reports | Median PFS 60 months; 2/5/10-year PFS 63%/50%/32%; 2/5/10-year OS 80%/63%/51%; age <65 years: median PFS 72 months, 5-year OS 82%; age ≥75 years: median PFS 36 months, 5-year OS 55%; 5-year OS improved to 91% in 2016-2020 vs 44% and 33% in earlier eras (cencini2024survivaloutcomesof pages 1-2, cencini2024survivaloutcomesof pages 3-5) | Improvement likely associated with wider BR use first line in elderly patients and ibrutinib second line; retrospective non-randomized cohort (cencini2024survivaloutcomesof pages 1-2, cencini2024survivaloutcomesof pages 3-5) | Jan 2024 | https://doi.org/10.3390/hematolrep16010006 | (cencini2024survivaloutcomesof pages 1-2, cencini2024survivaloutcomesof pages 3-5) |
| Frontline / population registry | Rituximab/cytarabine era registry outcomes | Binational registry study; Harmanen 2024 | Population-based cohort (n=564) had median OS about 80 months; 2-year OS 77%; 5-year OS 58%; 10-year OS 32%; POD24 identified as a strong poor-prognosis marker (cencini2024survivaloutcomesof pages 9-10, harmanen2024mantlecelllymphoma pages 144-152) | Reflects real-world heterogeneity across age/comorbidity; detailed regimen-specific toxicity not provided in excerpt (harmanen2024mantlecelllymphoma pages 144-152) | 2024 | Not available in provided context | (harmanen2024mantlecelllymphoma pages 144-152, cencini2024survivaloutcomesof pages 9-10) |
| Frontline intensive, real-world eligible/ineligible subsets | MCL2-like intensive cytarabine-containing approaches | Real-world registry analysis summarized in Harmanen 2024 | Trial-eligible patients treated with intensive MCL2-like regimens: median OS 14.3 years and median PFS about 6.4 years; trial-ineligible patients: median OS 9.8 years and median PFS about 4.4 years; Nordic MCL2 trial comparator median OS 12.7 years and PFS 8.5 years (harmanen2024mantlecelllymphoma pages 179-185) | Real-world expansion included older/frailer patients; retrospective comparisons subject to selection bias and incomplete subgroup reporting (harmanen2024mantlecelllymphoma pages 179-185) | 2024 | Not available in provided context | (harmanen2024mantlecelllymphoma pages 179-185) |
| Frontline / R/R supportive biologic strategies | Lenalidomide macrophage modulation; CD47 blockade + rituximab; bispecific antibodies (emerging) | 2024 tumor-microenvironment review; Nylund et al., Front Immunol | No practice-defining efficacy estimates provided in the excerpt for approval-level use in MCL; review notes lenalidomide can reduce CD163+ macrophages and enhance phagocytosis, and CD47 blockade plus rituximab can increase macrophage phagocytosis of MCL cells; bispecific antibodies described as promising next-step therapies rather than established standards (nylund2024empoweringmacrophagesthe pages 1-2, harmanen2024mantlecelllymphoma pages 60-66) | Avoid overstatement: these approaches are emerging/investigational or context-dependent in MCL, with efficacy and approval status still evolving in 2024 sources (nylund2024empoweringmacrophagesthe pages 1-2, harmanen2024mantlecelllymphoma pages 60-66) | Mar 2024 | https://doi.org/10.3389/fimmu.2024.1373269 | (nylund2024empoweringmacrophagesthe pages 1-2, harmanen2024mantlecelllymphoma pages 60-66) |
Table: This table summarizes key 2023-2024 treatment and real-world outcome evidence for mantle cell lymphoma across frontline and relapsed/refractory settings. It highlights pivotal CAR-T data, BTK inhibitor outcomes, registry survival trends, and emerging microenvironment-directed strategies with citations to the provided evidence context.
No validated primary prevention strategies were identified in the retrieved sources.
A real-world cohort description notes infection prophylaxis practices (e.g., HBV/HCV management; PCP prophylaxis) in clinical care contexts (cencini2024survivaloutcomesof pages 2-3). Additional guideline-level vaccination/prophylaxis details were not present in the retrieved excerpts.
No evidence on naturally occurring MCL in non-human species was retrieved in this run; thus not asserted.
No primary model-organism papers were retrieved in this run; thus model organism details (e.g., Eµ-CCND1 mice; xenografts; cell lines) cannot be cited here.
| Topic | Key facts (include quantitative where available) | Supporting recent source (include first author, year, journal) | PMID if known | URL | Evidence citation id(s) |
|---|---|---|---|---|---|
| Definition / rarity / age-sex | Mantle cell lymphoma (MCL) is a rare mature B-cell neoplasm arising from the mantle zone. It accounts for ~2–6% of all NHL in one 2024 registry source, with incidence commonly ~1 per 100,000 persons; Finnish 2021 data reported 102 new cases, incidence 1.63/100,000. Typical patients are older than 60 years, median age ~65, with male predominance >2:1. | Harmanen, 2024, registry study; López, 2024, Blood Advances | https://doi.org/10.1182/bloodadvances.2023011763 | (harmanen2024mantlecelllymphoma pages 31-34, lopez2024biologicalandclinical pages 1-2) | |
| Hallmark t(11;14) / CCND1 | The pathognomonic primary event is t(11;14)(q13;q32), usually IGH::CCND1, causing constitutive cyclin D1 overexpression. This lesion is present in >95% of classic/nodal MCL in one recent review and is preferentially detected by FISH in diagnostic workup. | López, 2024, Blood Advances; Ip, 2025, Cancers; Harmanen, 2024, registry study | https://doi.org/10.1182/bloodadvances.2023011763 | (lopez2024biologicalandclinical pages 1-2, ip2025updatesonthe pages 2-4, harmanen2024mantlecelllymphoma pages 34-39) | |
| Cyclin D1-negative cases | Cyclin D1-negative MCL is uncommon; recent reviews note rarer alternative cyclin-driven cases, including CCND2-rearranged disease, and emphasize SOX11 as particularly useful for identifying cyclin D1-negative MCL in practice. | López, 2024, Blood Advances; Ip, 2025, Cancers | https://doi.org/10.1182/bloodadvances.2023011763 | (lopez2024biologicalandclinical pages 1-2, ip2025updatesonthe pages 2-4) | |
| SOX11 | SOX11 is a key diagnostic and biologic marker. About 90% of MCL show nuclear SOX11 staining in one 2024 registry source; SOX11 IHC helps support diagnosis and subtype assignment, especially for cyclin D1-negative cases. Lack of SOX11 expression is linked to leukemic non-nodal/indolent presentations. | Harmanen, 2024, registry study; López, 2024, Blood Advances; Cencini, 2024, Hematology Reports | https://doi.org/10.1182/bloodadvances.2023011763 | (harmanen2024mantlecelllymphoma pages 31-34, lopez2024biologicalandclinical pages 1-2, cencini2024survivaloutcomesof pages 1-2) | |
| Molecular subtypes: cMCL vs nnMCL | Two main molecular/clinical subtypes are recognized: conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL). cMCL is typically SOX11+, often IGHV-unmutated, genomically more complex, and clinically more aggressive. nnMCL represents ~10–20% of cases, is often SOX11-negative, IGHV-mutated, genetically more stable, and may follow an indolent course, though some cases later progress. | López, 2024, Blood Advances; Harmanen, 2024, registry study; Cencini, 2024, Hematology Reports | https://doi.org/10.1182/bloodadvances.2023011763 | (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 31-34, cencini2024survivaloutcomesof pages 1-2) | |
| Pathways affected | MCL shows marked genomic instability affecting cell cycle control, cell survival, DNA damage response, telomere maintenance, NOTCH signaling, NF-κB/B-cell receptor signaling, and chromatin modification. Frequent recurrently altered genes include ATM, TP53, CDKN2A/B, and CCND1. | López, 2024, Blood Advances; Harmanen, 2024, registry study | https://doi.org/10.1182/bloodadvances.2023011763 | (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 34-39) | |
| Adverse prognostic factors | Recurrently adverse features include TP53 mutation/inactivation, CDKN2A/B loss/inactivation, high Ki-67/proliferation, blastoid or pleomorphic morphology, and high genetic complexity. Ki-67 >30% is cited as high-risk in one 2024 registry source; TP53 mutation is recommended for sequencing at diagnosis in 2024 guidance cited there. | López, 2024, Blood Advances; Harmanen, 2024, registry study | https://doi.org/10.1182/bloodadvances.2023011763 | (lopez2024biologicalandclinical pages 1-2, harmanen2024mantlecelllymphoma pages 34-39) | |
| Stage at diagnosis | Advanced presentation is typical. One 2023 review states >80% present with stage III/IV disease. In a 2024 real-life cohort, 84.9% had advanced-stage disease, including stage III 12.3% and stage IV 72.6%. | Kallam, 2023, Oncology; Cencini, 2024, Hematology Reports | https://doi.org/10.46883/2023.25921002 | (md2023currenttreatmentsin pages 12-13, cencini2024survivaloutcomesof pages 3-5) |
Table: This table condenses key mantle cell lymphoma biology, subtype distinctions, diagnostic markers, and adverse prognostic features from recent sources. It is useful as a knowledge-base-ready snapshot linking core facts to supporting evidence and URLs.
Cropped figures/tables were retrieved from the ZUMA-2 3-year follow-up paper showing the key efficacy endpoints and MRD-related summaries (wang2023threeyearfollowupof media 7705478f, wang2023threeyearfollowupof media 514e8505, wang2023threeyearfollowupof media d297d7b8, wang2023threeyearfollowupof media 87d7a7f7).
References
(harmanen2024mantlecelllymphoma pages 31-34): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(lopez2024biologicalandclinical pages 1-2): Cristina López, Elisabeth Silkenstedt, Martin Dreyling, and Sílvia Beà. Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma. Blood Advances, 8:3652-3664, Jul 2024. URL: https://doi.org/10.1182/bloodadvances.2023011763, doi:10.1182/bloodadvances.2023011763. This article has 19 citations and is from a peer-reviewed journal.
(cencini2024survivaloutcomesof pages 1-2): Emanuele Cencini, Natale Calomino, Marta Franceschini, Andreea Dragomir, Sara Fredducci, Beatrice Esposito Vangone, Giulia Lucco Navei, Alberto Fabbri, and Monica Bocchia. Survival outcomes of patients with mantle cell lymphoma: a retrospective, 15-year, real-life study. Hematology Reports, 16:50-62, Jan 2024. URL: https://doi.org/10.3390/hematolrep16010006, doi:10.3390/hematolrep16010006. This article has 17 citations.
(md2023currenttreatmentsin pages 12-13): Avyakta Kallam Md and J. Vose. Current treatments in mantle cell lymphoma. Oncology, 37 8:326-333, Aug 2023. URL: https://doi.org/10.46883/2023.25921002, doi:10.46883/2023.25921002. This article has 2 citations and is from a peer-reviewed journal.
(harmanen2024mantlecelllymphoma pages 24-31): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(ip2025updatesonthe pages 20-21): Andrew Ip, Maciej Kabat, Lindsay Fogel, Hassan Alkhatatneh, Jason Voss, Amolika Gupta, Alexandra Della Pia, Lori A. Leslie, Tatyana Feldman, Maher Albitar, and Andre H. Goy. Updates on the biological heterogeneity of mantle cell lymphoma. Cancers, 17:696, Feb 2025. URL: https://doi.org/10.3390/cancers17040696, doi:10.3390/cancers17040696. This article has 3 citations.
(cencini2024survivaloutcomesof pages 3-5): Emanuele Cencini, Natale Calomino, Marta Franceschini, Andreea Dragomir, Sara Fredducci, Beatrice Esposito Vangone, Giulia Lucco Navei, Alberto Fabbri, and Monica Bocchia. Survival outcomes of patients with mantle cell lymphoma: a retrospective, 15-year, real-life study. Hematology Reports, 16:50-62, Jan 2024. URL: https://doi.org/10.3390/hematolrep16010006, doi:10.3390/hematolrep16010006. This article has 17 citations.
(harmanen2024mantlecelllymphoma pages 60-66): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(harmanen2024mantlecelllymphoma pages 34-39): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(nylund2024empoweringmacrophagesthe pages 1-2): Patrick Nylund, Anna Nikkarinen, Sara Ek, and Ingrid Glimelius. Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma. Frontiers in Immunology, Mar 2024. URL: https://doi.org/10.3389/fimmu.2024.1373269, doi:10.3389/fimmu.2024.1373269. This article has 7 citations and is from a peer-reviewed journal.
(lopez2024biologicalandclinical pages 12-13): Cristina López, Elisabeth Silkenstedt, Martin Dreyling, and Sílvia Beà. Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma. Blood Advances, 8:3652-3664, Jul 2024. URL: https://doi.org/10.1182/bloodadvances.2023011763, doi:10.1182/bloodadvances.2023011763. This article has 19 citations and is from a peer-reviewed journal.
(harmanen2024mantlecelllymphoma pages 144-152): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(wang2023threeyearfollowupof pages 1-2): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(wang2023threeyearfollowupof pages 3-4): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(wang2023threeyearfollowupof pages 2-3): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(cencini2024survivaloutcomesof pages 2-3): Emanuele Cencini, Natale Calomino, Marta Franceschini, Andreea Dragomir, Sara Fredducci, Beatrice Esposito Vangone, Giulia Lucco Navei, Alberto Fabbri, and Monica Bocchia. Survival outcomes of patients with mantle cell lymphoma: a retrospective, 15-year, real-life study. Hematology Reports, 16:50-62, Jan 2024. URL: https://doi.org/10.3390/hematolrep16010006, doi:10.3390/hematolrep16010006. This article has 17 citations.
(wang2023threeyearfollowupof pages 9-10): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(cencini2024survivaloutcomesof pages 9-10): Emanuele Cencini, Natale Calomino, Marta Franceschini, Andreea Dragomir, Sara Fredducci, Beatrice Esposito Vangone, Giulia Lucco Navei, Alberto Fabbri, and Monica Bocchia. Survival outcomes of patients with mantle cell lymphoma: a retrospective, 15-year, real-life study. Hematology Reports, 16:50-62, Jan 2024. URL: https://doi.org/10.3390/hematolrep16010006, doi:10.3390/hematolrep16010006. This article has 17 citations.
(harmanen2024mantlecelllymphoma pages 179-185): M Harmanen. Mantle cell lymphoma in the rituximab era: retrospective registry study on survival, treatment and prognostic factors. Unknown journal, 2024.
(ip2025updatesonthe pages 2-4): Andrew Ip, Maciej Kabat, Lindsay Fogel, Hassan Alkhatatneh, Jason Voss, Amolika Gupta, Alexandra Della Pia, Lori A. Leslie, Tatyana Feldman, Maher Albitar, and Andre H. Goy. Updates on the biological heterogeneity of mantle cell lymphoma. Cancers, 17:696, Feb 2025. URL: https://doi.org/10.3390/cancers17040696, doi:10.3390/cancers17040696. This article has 3 citations.
(wang2023threeyearfollowupof media 7705478f): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(wang2023threeyearfollowupof media 514e8505): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(wang2023threeyearfollowupof media d297d7b8): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
(wang2023threeyearfollowupof media 87d7a7f7): Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron A. Jacobson, Brian T. Hill, John M. Timmerman, Houston Holmes, Samantha Jaglowski, Ian W. Flinn, Peter A. McSweeney, David B. Miklos, John M. Pagel, Marie José Kersten, Krimo Bouabdallah, Rashmi Khanal, Max S. Topp, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine R. Shen, Rubina Siddiqi, Ioana Kloos, and Patrick M. Reagan. Three-year follow-up of kte-x19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the zuma-2 study. Journal of Clinical Oncology, 41:555-567, Jan 2023. URL: https://doi.org/10.1200/jco.21.02370, doi:10.1200/jco.21.02370. This article has 354 citations and is from a highest quality peer-reviewed journal.
name: Mantle Cell Lymphoma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-11T21:17:25Z'
synonyms:
- MCL
- mantle-cell lymphoma
description: >-
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized
by the t(11;14)(q13;q32) translocation, which juxtaposes the CCND1 (cyclin D1) gene
with the immunoglobulin heavy chain enhancer, leading to constitutive cyclin D1
overexpression. MCL typically presents at advanced stage with lymphadenopathy,
bone marrow involvement, and frequently gastrointestinal tract infiltration. While
historically considered incurable with median survival of 3-5 years, outcomes have
improved with BTK inhibitors (ibrutinib, acalabrutinib), high-dose therapy with
stem cell transplant in younger patients, and emerging therapies including CAR-T
cells.
definitions:
- name: Pathologic definition of mantle cell lymphoma
definition_type: CASE_DEFINITION
description: >-
Mantle cell lymphoma is a mature B-cell non-Hodgkin lymphoma usually
characterized by t(11;14)(q13;q32), or CCND1 translocation, and cyclin D1
overexpression.
scope: General pathologic and clinical definition of mantle cell lymphoma
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma usually characterized by t(11;14) (q13;q32), or CCND1 translocation and Cyclin D1 over expression."
explanation: This review provides a concise disease-level definition anchored to the defining cytogenetic and protein-expression features of mantle cell lymphoma.
categories:
- Hematologic Malignancy
- B-cell Neoplasm
- Non-Hodgkin Lymphoma
parents:
- B-cell non-Hodgkin lymphoma
has_subtypes:
- name: Classical Mantle Cell Lymphoma
description: >-
The predominant form characterized by monotonous small to medium-sized
lymphocytes with irregular nuclear contours. Typically presents with
widespread nodal and extranodal disease. Aggressive clinical course
requiring treatment.
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior."
explanation: This supports conventional/classical MCL as one of the 2 major molecular and clinical subtypes of mantle cell lymphoma.
- name: Leukemic Non-Nodal Mantle Cell Lymphoma
description: >-
Indolent variant presenting with splenomegaly, bone marrow involvement,
and peripheral blood disease without significant lymphadenopathy.
Often SOX11-negative with IGHV mutations. May be managed with
observation initially.
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior."
explanation: This supports leukemic non-nodal MCL as a recognized major subtype distinct from conventional MCL.
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "However, indolent variants, including in situ mantle cell neoplasm and the recently recognized leukemic non-nodal MCL do exist."
explanation: This specifically supports leukemic non-nodal MCL as an indolent recognized variant.
- name: Blastoid Mantle Cell Lymphoma
description: >-
Aggressive morphologic variant with blastoid or pleomorphic features,
high proliferation rate, and worse prognosis. May arise de novo or
from transformation of classical MCL. Often harbors TP53 mutations.
evidence:
- reference: PMID:33091144
reference_title: "Palatine Tonsils Primary Presentation of Blastoid Variant of Mantle Cell Lymphoma: Case Report."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The blastoid variant of mantle cell lymphoma (MCL) accounts for less than one-third of all MCL cases."
explanation: This supports blastoid mantle cell lymphoma as a recognized morphologic subtype within the mantle cell lymphoma spectrum.
epidemiology:
- name: Relative frequency among lymphoid neoplasms
description: >-
Mantle cell lymphoma is an uncommon lymphoma subtype, representing a small
minority of all lymphoid neoplasms.
unit: percent of lymphoid neoplasms
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle-cell lymphoma (MCL) is a well-defined subtype of B-cell non-Hodgkin's lymphomas (B-NHL), accounts for approximately 6% of all lymphoid neoplasms, and has a median survival of 3 to 4 years."
explanation: This review quantifies MCL as an uncommon lymphoma subtype comprising about 6% of lymphoid neoplasms.
prevalence:
- population: All lymphoma diagnoses
percentage: 3-10
evidence:
- reference: PMID:21850989
reference_title: "Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL; previously called centrocytic lymphoma or lymphocytic lymphoma of intermediate differentiation) is a distinct subtype of B-cell lymphoma, accounting for approximately 3%-10% of all lymphoma diagnoses."
explanation: This review provides a prevalence-style estimate of the proportion of all lymphoma diagnoses represented by mantle cell lymphoma.
- population: All lymphoid neoplasms
percentage: 6
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle-cell lymphoma (MCL) is a well-defined subtype of B-cell non-Hodgkin's lymphomas (B-NHL), accounts for approximately 6% of all lymphoid neoplasms, and has a median survival of 3 to 4 years."
explanation: This review supports a complementary estimate that mantle cell lymphoma comprises about 6% of lymphoid neoplasms.
pathophysiology:
- name: CCND1/IGH translocation
description: >-
The defining t(11;14)(q13;q32) rearrangement juxtaposes CCND1 with
immunoglobulin heavy-chain regulatory elements in mantle cell lymphoma cells.
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to deregulation and upregulation of Cyclin D1, an important regulator of the G1 phase of the cell cycle."
explanation: This review defines t(11;14) as the hallmark initiating genetic lesion in mantle cell lymphoma.
cell_types:
- preferred_term: B cell
term:
id: CL:0000236
label: B cell
downstream:
- target: Cyclin D1 overexpression
description: The rearrangement places CCND1 under enhancer control and drives constitutive cyclin D1 expression.
causal_link_type: DIRECT
evidence:
- reference: PMID:19556426
reference_title: "How I treat mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma is included in the World Health Organization classification as distinct lymphoma subtype characterized by the t(11;14)(q13;q32) translocation, which results in overexpression of Cyclin D1."
explanation: This directly supports the causal transition from t(11;14) to cyclin D1 overexpression.
- name: Cyclin D1 overexpression
description: >-
Constitutive cyclin D1 expression is the canonical biochemical consequence
of the CCND1 rearrangement and removes normal restraint on G1-phase control.
evidence:
- reference: PMID:19556426
reference_title: "How I treat mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma is included in the World Health Organization classification as distinct lymphoma subtype characterized by the t(11;14)(q13;q32) translocation, which results in overexpression of Cyclin D1."
explanation: This supports cyclin D1 overexpression as the immediate downstream consequence of the defining translocation.
downstream:
- target: G1/S cell-cycle acceleration
description: Excess cyclin D1 deregulates the G1 checkpoint and promotes entry into S phase.
causal_link_type: DIRECT
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to deregulation and upregulation of Cyclin D1, an important regulator of the G1 phase of the cell cycle."
explanation: This supports cyclin D1 overexpression as a mechanistic driver of G1-phase dysregulation.
- name: G1/S cell-cycle acceleration
description: >-
Cyclin D1-driven checkpoint escape accelerates G1-to-S progression and
sustains the proliferative program of malignant mantle-zone B cells.
biological_processes:
- preferred_term: G1/S transition of mitotic cell cycle
modifier: INCREASED
term:
id: GO:0000082
label: G1/S transition of mitotic cell cycle
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to deregulation and upregulation of Cyclin D1, an important regulator of the G1 phase of the cell cycle."
explanation: This supports accelerated G1/S control as a core cell-cycle consequence of the mantle cell lymphoma genetic hallmark.
downstream:
- target: Malignant B-cell expansion
description: Faster cell-cycle transit increases accumulation of neoplastic B cells.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- CDK4/6 activation
- retinoblastoma pathway bypass
evidence:
- reference: PMID:20940415
reference_title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability."
explanation: This supports accelerated cell-cycle progression as a core driver of downstream accumulation of mantle cell lymphoma cells.
- name: DNA damage response pathway inactivation
description: >-
Secondary lesions involving ATM, CHK1/CHK2, TP53, and related checkpoint
regulators weaken the normal response to DNA damage in mantle cell lymphoma.
evidence:
- reference: PMID:20940415
reference_title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways."
explanation: This supports DNA damage response inactivation as a distinct secondary mechanistic branch in MCL pathogenesis.
downstream:
- target: Genetic instability
description: Loss of checkpoint control permits ongoing accumulation of structural and sequence alterations.
causal_link_type: DIRECT
evidence:
- reference: PMID:20940415
reference_title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways. In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability."
explanation: This directly supports the transition from impaired DNA damage response to pronounced genetic instability.
- name: Genetic instability
description: >-
Complex secondary genomic alterations accumulate as checkpoint failure and
cell-cycle dysregulation reinforce clonal diversification and biologic
aggressiveness.
evidence:
- reference: PMID:20940415
reference_title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Secondary genetic events increase the oncogenic potential of cyclin D1 and frequently inactivate DNA damage response pathways. In combination these changes drive cell-cycle progression and give rise to pronounced genetic instability."
explanation: This supports genetic instability as a discrete downstream state in mantle cell lymphoma.
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "An increasing genomic complexity, together with the presence of breakage-fusion-bridge cycles and high DNA methylation changes related to the proliferative cell history, defines patients with different clinical evolution."
explanation: This large genomic study supports genetic complexity as a clinically relevant property of mantle cell lymphoma clones.
downstream:
- target: Malignant B-cell expansion
description: Genetically complex clones gain fitness advantages that support continued accumulation of lymphoma cells.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- clonal selection
- acquisition of additional driver lesions
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "An increasing genomic complexity, together with the presence of breakage-fusion-bridge cycles and high DNA methylation changes related to the proliferative cell history, defines patients with different clinical evolution."
explanation: This partially supports the edge by linking greater genomic complexity to the clinically evolving, more proliferative mantle cell lymphoma state.
- name: Microenvironmental crosstalk in marrow and secondary lymphoid organs
description: >-
Mantle cell lymphoma cells occupy supportive niches in bone marrow and
secondary lymphoid organs where adhesion molecules and soluble factors shape
lymphoma-cell behavior.
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
- preferred_term: lymph node
term:
id: UBERON:0000029
label: lymph node
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "MCL cells develop in specialized tissue microenvironments such as bone marrow and secondary lymphoid organs, where the pathological cells interact with several microenvironmental components through a complex network of soluble factors and adhesion molecules."
explanation: This supports a distinct microenvironmental mechanism operating in marrow and lymphoid tissue niches.
downstream:
- target: B-cell receptor signaling activation
description: Niche-dependent cues reinforce ongoing B-cell receptor signaling in mantle cell lymphoma cells.
causal_link_type: DIRECT
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This dynamic and complex system, including the activation of B-cell receptor signaling (BCR), promotes survival, immune evasion, and therapeutic resistance."
explanation: This supports the transition from microenvironmental crosstalk to activation of BCR signaling.
- name: B-cell receptor signaling activation
description: >-
Activated B-cell receptor signaling is a central prosurvival program in
mantle cell lymphoma and helps integrate external cues from the tumor
microenvironment.
biological_processes:
- preferred_term: B cell activation
modifier: INCREASED
term:
id: GO:0042113
label: B cell activation
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This dynamic and complex system, including the activation of B-cell receptor signaling (BCR), promotes survival, immune evasion, and therapeutic resistance."
explanation: This supports ongoing BCR pathway activation as a central mantle cell lymphoma mechanism.
downstream:
- target: B-cell survival advantage
description: BCR pathway output sustains survival signaling in neoplastic B lymphocytes.
causal_link_type: DIRECT
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Given the central role of the BCR signaling pathway in proliferation and survival of neoplastic B lymphocytes, in the last decades several biological agents against the key BCR proteins, i.e. Bruton Tyrosine Kinase inhibitors (BTKi), have been developed, and they represent the most effective treatment for MCL management."
explanation: This directly supports BCR signaling as a driver of survival in neoplastic B lymphocytes.
- name: B-cell survival advantage
description: >-
Integrated prosurvival signaling reduces apoptotic restraint and helps mantle
cell lymphoma clones persist within supportive tissue niches.
biological_processes:
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Given the central role of the BCR signaling pathway in proliferation and survival of neoplastic B lymphocytes, in the last decades several biological agents against the key BCR proteins, i.e. Bruton Tyrosine Kinase inhibitors (BTKi), have been developed, and they represent the most effective treatment for MCL management."
explanation: This supports a discrete survival-advantage state downstream of BCR signaling.
downstream:
- target: Malignant B-cell expansion
description: Reduced cell death allows continued net accumulation of lymphoma cells.
causal_link_type: DIRECT
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Given the central role of the BCR signaling pathway in proliferation and survival of neoplastic B lymphocytes, in the last decades several biological agents against the key BCR proteins, i.e. Bruton Tyrosine Kinase inhibitors (BTKi), have been developed, and they represent the most effective treatment for MCL management."
explanation: This supports the transition from prosurvival signaling to expansion of neoplastic B cells.
- name: Malignant B-cell expansion
description: >-
Combined cell-cycle acceleration, survival signaling, and genetic complexity
support net accumulation of neoplastic mantle-zone B cells over time.
cell_types:
- preferred_term: B cell
term:
id: CL:0000236
label: B cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:41219853
reference_title: "B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Given the central role of the BCR signaling pathway in proliferation and survival of neoplastic B lymphocytes, in the last decades several biological agents against the key BCR proteins, i.e. Bruton Tyrosine Kinase inhibitors (BTKi), have been developed, and they represent the most effective treatment for MCL management."
explanation: This supports proliferative expansion of neoplastic B lymphocytes as a central downstream state in MCL.
downstream:
- target: Widespread tissue infiltration by malignant B cells
description: Progressive clonal accumulation ultimately presents as advanced-stage nodal and extranodal disease.
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- homing to supportive niches
- extranodal dissemination
evidence:
- reference: PMID:19863180
reference_title: "Mantle cell lymphoma: state-of-the-art management and future perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Most patients present with advanced stage disease, often with extranodal dissemination, and typically pursue an aggressive clinical course."
explanation: This supports malignant clonal expansion culminating in disseminated advanced-stage mantle cell lymphoma.
- name: Widespread tissue infiltration by malignant B cells
description: >-
Mantle cell lymphoma commonly presents as advanced-stage disease with both
nodal and extranodal involvement, especially in bone marrow and the
gastrointestinal tract.
locations:
- preferred_term: lymph node
term:
id: UBERON:0000029
label: lymph node
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
cell_types:
- preferred_term: B cell
term:
id: CL:0000236
label: B cell
evidence:
- reference: PMID:19863180
reference_title: "Mantle cell lymphoma: state-of-the-art management and future perspective."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Most patients present with advanced stage disease, often with extranodal dissemination, and typically pursue an aggressive clinical course."
explanation: This supports advanced-stage disseminated disease as a characteristic downstream pathobiologic state in mantle cell lymphoma.
- reference: PMID:19556426
reference_title: "How I treat mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The clinical presentation often includes extranodal involvement, particularly of the bone marrow and gut."
explanation: This review specifically supports bone marrow and gastrointestinal involvement as common sites of mantle cell lymphoma dissemination.
downstream:
- target: Generalized Lymphadenopathy
description: Disseminated nodal accumulation of lymphoma cells manifests clinically as widespread lymph node enlargement.
causal_link_type: DIRECT
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients."
explanation: This directly supports generalized lymphadenopathy as a clinical consequence of disseminated mantle cell lymphoma.
- target: Splenomegaly
description: Lymphomatous splenic involvement produces clinically apparent enlargement of the spleen.
causal_link_type: DIRECT
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients."
explanation: This supports splenomegaly as a common clinical outcome of disseminated mantle cell lymphoma.
- target: Gastrointestinal Involvement
description: Extranodal infiltration of the gut manifests as mantle cell lymphoma involvement of the gastrointestinal tract.
causal_link_type: DIRECT
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients."
explanation: This directly supports gastrointestinal involvement as a downstream clinical manifestation of widespread mantle cell lymphoma infiltration.
histopathology:
- name: Mature B-Cell Lymphoma
finding_term:
preferred_term: Mature B-Cell Non-Hodgkin Lymphoma
term:
id: NCIT:C7056
label: Mature B-Cell Non-Hodgkin Lymphoma
frequency: VERY_FREQUENT
description: Mantle cell lymphoma is a mature B-cell non-Hodgkin lymphoma.
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma usually"
explanation: Abstract describes mantle cell lymphoma as a mature B-cell non-Hodgkin lymphoma.
phenotypes:
- category: Lymphatic
name: Generalized Lymphadenopathy
frequency: VERY_FREQUENT
description: >-
Widespread lymph node enlargement is the most common presentation.
Multiple nodal sites are typically involved at diagnosis.
phenotype_term:
preferred_term: Generalized lymphadenopathy
term:
id: HP:0008940
label: Generalized lymphadenopathy
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%"
explanation: This review supports generalized lymphadenopathy as the dominant presenting clinical phenotype of mantle cell lymphoma.
- category: Abdominal
name: Splenomegaly
frequency: VERY_FREQUENT
description: >-
Spleen enlargement is common, particularly prominent in the leukemic
non-nodal variant.
phenotype_term:
preferred_term: Splenomegaly
term:
id: HP:0001744
label: Splenomegaly
evidence:
- reference: PMID:15370245
reference_title: "The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Presenting features included splenomegaly (74%), lymphadenopathy (45%), hepatomegaly (17%)"
explanation: This leukemic-presentation cohort directly supports splenomegaly as a common presenting manifestation of mantle cell lymphoma.
- category: Abdominal
name: Hepatomegaly
frequency: OCCASIONAL
description: >-
Liver enlargement is a recognized manifestation of disseminated mantle cell
lymphoma, particularly in advanced leukemic or extranodal presentations.
phenotype_term:
preferred_term: Hepatomegaly
term:
id: HP:0002240
label: Hepatomegaly
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients."
explanation: This clinical review supports hepatomegaly as a recurrent though less dominant manifestation of mantle cell lymphoma.
- category: Gastrointestinal
name: Gastrointestinal Involvement
frequency: FREQUENT
description: >-
MCL has a propensity for gastrointestinal tract involvement with
lymphomatous polyposis. Colonoscopy may reveal multiple polyps.
phenotype_term:
preferred_term: Neoplasm of the gastrointestinal tract
term:
id: HP:0007378
label: Neoplasm of the gastrointestinal tract
evidence:
- reference: PMID:17001159
reference_title: "Gastrointestinal involvement in mantle cell lymphoma: a prospective clinic, endoscopic, and pathologic study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "As a whole, 92% of patients showed upper or lower GI tract infiltration by MCL."
explanation: This prospective endoscopic study demonstrates that GI tract involvement is extremely common in MCL when systematically evaluated.
- category: Constitutional
name: Fever
frequency: FREQUENT
description: >-
Fever is part of the B-symptom spectrum and reflects systemic mantle cell
lymphoma activity at presentation.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
evidence:
- reference: PMID:38222137
reference_title: "Mantle Cell Lymphoma Presenting as Cholecystitis and Nephromegaly."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) most commonly presents as lymphadenopathy (LAD), fevers, night sweats, weight loss, splenomegaly, and blood count abnormalities."
explanation: This clinical report explicitly lists fever among the common presenting manifestations of mantle cell lymphoma.
- category: Constitutional
name: Night Sweats
frequency: FREQUENT
description: >-
B symptoms including night sweats are common and indicate
systemic disease activity.
phenotype_term:
preferred_term: Night sweats
term:
id: HP:0030166
label: Night sweats
evidence:
- reference: PMID:38222137
reference_title: "Mantle Cell Lymphoma Presenting as Cholecystitis and Nephromegaly."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) most commonly presents as lymphadenopathy (LAD), fevers, night sweats, weight loss, splenomegaly, and blood count abnormalities."
explanation: This clinical report explicitly lists night sweats among the common presenting manifestations of mantle cell lymphoma.
- category: Constitutional
name: Weight Loss
frequency: FREQUENT
description: >-
Unintentional weight loss is a B symptom indicating active disease.
phenotype_term:
preferred_term: Weight loss
term:
id: HP:0001824
label: Weight loss
evidence:
- reference: PMID:38222137
reference_title: "Mantle Cell Lymphoma Presenting as Cholecystitis and Nephromegaly."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) most commonly presents as lymphadenopathy (LAD), fevers, night sweats, weight loss, splenomegaly, and blood count abnormalities."
explanation: This clinical report explicitly includes weight loss among the common presenting features of mantle cell lymphoma.
- category: Constitutional
name: Fatigue
frequency: VERY_FREQUENT
description: >-
Fatigue from disease burden and anemia.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
evidence:
- reference: PMID:15914363
reference_title: "Complete and durable remission of refractory mantle cell lymphoma with repeated rituximab monotherapy."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We encountered a 53-year-old man with general fatigue."
explanation: This case report supports fatigue as a clinically relevant presenting symptom in mantle cell lymphoma, although it does not establish frequency.
- category: Hematologic
name: Anemia
frequency: FREQUENT
description: >-
Anemia from bone marrow infiltration is common given the high
frequency of marrow involvement at diagnosis.
phenotype_term:
preferred_term: Anemia
term:
id: HP:0001903
label: Anemia
evidence:
- reference: PMID:15370245
reference_title: "The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Median lymphocyte count was 58 x 10(9)/l, 55% had anemia and 17% had thrombocytopenia."
explanation: This leukemic mantle cell lymphoma cohort directly supports anemia as a common hematologic manifestation.
- category: Hematologic
name: Peripheral Blood Lymphocytosis
frequency: OCCASIONAL
description: >-
Elevated circulating lymphocyte counts occur in a subset of mantle cell
lymphoma cases, especially leukemic presentations.
phenotype_term:
preferred_term: Peripheral blood lymphocytosis
term:
id: HP:0100827
label: Increased total lymphocyte count
evidence:
- reference: PMID:9178843
reference_title: "Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic problems."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Initial parameters in all published series are advanced disease with generalized lymphadenopathy in 90%, bone marrow infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%, gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in 20-30% of patients."
explanation: This review supports peripheral blood lymphocytosis as a recognized hematologic manifestation in a subset of mantle cell lymphoma patients.
- category: Hematologic
name: Thrombocytopenia
frequency: OCCASIONAL
description: >-
Platelet reduction can accompany leukemic mantle cell lymphoma, reflecting
marrow involvement or advanced hematologic disease burden.
phenotype_term:
preferred_term: Thrombocytopenia
term:
id: HP:0001873
label: Thrombocytopenia
evidence:
- reference: PMID:15370245
reference_title: "The leukemic presentation of mantle-cell lymphoma: disease features and prognostic factors in 58 patients."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Median lymphocyte count was 58 x 10(9)/l, 55% had anemia and 17% had thrombocytopenia."
explanation: This leukemic mantle cell lymphoma cohort directly supports thrombocytopenia as an associated hematologic manifestation.
biochemical:
- name: Cyclin D1 Expression
notes: >-
Immunohistochemistry for cyclin D1 (CCND1) is positive in virtually all MCL
cases and is essential for diagnosis. SOX11 expression helps distinguish
classical from leukemic non-nodal variants.
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma usually characterized by t(11;14) (q13;q32), or CCND1 translocation and Cyclin D1 over expression."
explanation: This supports cyclin D1 overexpression as a core biochemical and diagnostic feature of mantle cell lymphoma.
- name: Flow Cytometry Immunophenotyping
notes: >-
MCL cells are CD5+, CD19+, CD20+, CD23-, FMC7+, with moderate to strong
surface immunoglobulin. The CD5+ CD23- phenotype helps distinguish from
CLL which is typically CD23+.
evidence:
- reference: PMID:19846810
reference_title: "Immunophenotypic variations in mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) expresses pan-B-cell antigens and is usually CD5+/CD10-/CD23-/FMC7+."
explanation: This study directly supports the typical CD5-positive, CD23-negative, FMC7-positive immunophenotype used in flow-cytometric recognition of mantle cell lymphoma.
- reference: PMID:7713480
reference_title: "Mantle cell lymphoma: a clinicopathological study of 55 cases."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23."
explanation: This clinicopathologic series independently supports the characteristic mantle cell lymphoma immunophenotype and its diagnostic utility.
genetic:
- name: CCND1/IGH Translocation
association: Defining Genetic Lesion
gene_term:
preferred_term: CCND1
term:
id: hgnc:1582
label: CCND1
notes: >-
The t(11;14)(q13;q32) translocation is the hallmark of MCL, present in
virtually all cases. It places CCND1 under IGH enhancer control, causing
cyclin D1 overexpression. Detected by FISH, karyotype, or cyclin D1 IHC.
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to deregulation and upregulation of Cyclin D1, an important regulator of the G1 phase of the cell cycle."
explanation: This directly supports CCND1/IGH translocation as the defining genetic lesion of mantle cell lymphoma.
- name: TP53 Mutation
association: Adverse Prognostic Marker
gene_term:
preferred_term: TP53
term:
id: hgnc:11998
label: TP53
notes: >-
TP53 mutations occur in 20-30% of MCL and are associated with aggressive
biology, blastoid morphology, and poor response to chemotherapy. May
retain sensitivity to BTK inhibitors and novel agents.
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Several drivers had prognostic impact, but only TP53 and MYC aberrations added value independently of genomic complexity."
explanation: This supports TP53 aberration as an adverse prognostic marker with independent impact in mantle cell lymphoma.
- name: ATM Mutation/Deletion
association: Intermediate-Risk Marker
gene_term:
preferred_term: ATM
term:
id: hgnc:795
label: ATM
notes: >-
ATM abnormalities occur in 40-50% of MCL and impair DNA damage responses.
Associated with genomic instability and disease progression.
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "cMCL carried significant higher numbers of structural variants, copy number alterations, and driver changes than nnMCL, with exclusive alterations of ATM in cMCL"
explanation: This supports ATM alteration as a recurrent genomic event in conventional mantle cell lymphoma linked to genomic instability.
diagnosis:
- name: Tissue biopsy with morphologic and immunophenotypic assessment
description: >-
Diagnosis is established on involved tissue using morphologic review
together with immunophenotypic characterization to distinguish mantle cell
lymphoma from other small B-cell lymphomas.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: MAXO:0000003
label: diagnostic procedure
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This review will focus on the pathologic diagnosis of MCL using the traditional morphological and immunophenotypic strategies combined with cytogenetic characteristics and recently identified molecular profile."
explanation: This supports tissue-based morphologic and immunophenotypic assessment as the core diagnostic approach for mantle cell lymphoma.
- name: Molecular genetic testing for CCND1 rearrangement
description: >-
Molecular confirmation of t(11;14)/CCND1 rearrangement is highly supportive
of mantle cell lymphoma and helps resolve diagnostically challenging cases.
diagnosis_term:
preferred_term: molecular genetic testing
term:
id: MAXO:0000533
label: molecular genetic testing
qualifiers:
- predicate:
preferred_term: has participant
term:
id: RO:0000057
label: has participant
value:
preferred_term: CCND1
term:
id: hgnc:1582
label: CCND1
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma usually characterized by t(11;14) (q13;q32), or CCND1 translocation and Cyclin D1 over expression."
explanation: This supports molecular detection of CCND1 rearrangement as a defining diagnostic feature of mantle cell lymphoma.
differential_diagnoses:
- name: B-cell Chronic Lymphocytic Leukemia
disease_term:
preferred_term: B-cell chronic lymphocytic leukemia
term:
id: MONDO:0004948
label: B-cell chronic lymphocytic leukemia
description: >-
Small B-cell neoplasm that can overlap with mantle cell lymphoma on routine
morphology and blood or marrow involvement, but typically differs in
immunophenotype and lacks the defining CCND1 rearrangement of MCL.
distinguishing_features:
- CLL usually shows a CD23-positive immunophenotype, unlike the typical CD23-negative pattern of mantle cell lymphoma.
- Mantle cell lymphoma is defined by t(11;14)/CCND1 dysregulation and often uses SOX11 or CD200 to resolve diagnostic uncertainty.
evidence:
- reference: PMID:21850989
reference_title: "Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Pitfalls in the differential diagnosis versus B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will be discussed, including the usefulness new diagnostic markers SOX11 and CD200."
explanation: This pathology review explicitly identifies B-cell chronic lymphocytic leukemia as an important diagnostic pitfall in mantle cell lymphoma.
- name: B-cell Prolymphocytic Leukemia
disease_term:
preferred_term: B-cell prolymphocytic leukemia
term:
id: MONDO:0019461
label: B-cell prolymphocytic leukemia
description: >-
Leukemic mature B-cell neoplasm that may resemble mantle cell lymphoma in
blood-based presentations but has a different cytologic appearance and does
not share the canonical CCND1-driven mantle cell lymphoma program.
distinguishing_features:
- B-PLL is dominated by circulating prolymphocytes rather than the typical mantle cell lymphoma morphologic spectrum.
- Demonstration of CCND1 rearrangement or cyclin D1 overexpression supports mantle cell lymphoma over B-PLL.
evidence:
- reference: PMID:21850989
reference_title: "Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Pitfalls in the differential diagnosis versus B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will be discussed, including the usefulness new diagnostic markers SOX11 and CD200."
explanation: This review explicitly includes B-cell prolymphocytic leukemia among the key differential diagnoses of mantle cell lymphoma.
- name: Diffuse Large B-cell Lymphoma
disease_term:
preferred_term: diffuse large B-cell lymphoma
term:
id: MONDO:0018905
label: diffuse large B-cell lymphoma
description: >-
Aggressive large-cell lymphoma that enters the differential diagnosis when
mantle cell lymphoma shows blastoid morphology or cyclin D1 expression in a
large-cell pattern.
distinguishing_features:
- DLBCL is composed of large transformed B cells, whereas classic MCL shows small to medium-sized cells and blastoid MCL remains CCND1-driven.
- Cyclin D1-positive DLBCL is a specific diagnostic pitfall that requires integrated morphologic and molecular review.
evidence:
- reference: PMID:21850989
reference_title: "Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Pitfalls in the differential diagnosis versus B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will be discussed, including the usefulness new diagnostic markers SOX11 and CD200."
explanation: This review specifically identifies cyclin D1-positive diffuse large B-cell lymphoma as a differential-diagnostic pitfall for mantle cell lymphoma.
- name: Hairy Cell Leukemia
disease_term:
preferred_term: hairy cell leukemia
term:
id: MONDO:0018935
label: hairy cell leukemia
description: >-
Mature B-cell leukemia that can overlap with splenic and marrow-based mantle
cell lymphoma presentations but is distinguished by its characteristic hairy
cytology and separate immunophenotypic profile.
distinguishing_features:
- Hairy cell leukemia has characteristic cytoplasmic projections and a different immunophenotypic signature than mantle cell lymphoma.
- SOX11 and CD200 can help resolve specific diagnostic pitfalls when morphology and basic markers are not definitive.
evidence:
- reference: PMID:21850989
reference_title: "Mantle cell lymphoma: recent insights into pathogenesis, clinical variability, and new diagnostic markers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Pitfalls in the differential diagnosis versus B-cell chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, cyclin D1-positive diffuse large B-cell lymphoma, hairy cell leukemia, and plasma cell tumors will be discussed, including the usefulness new diagnostic markers SOX11 and CD200."
explanation: This review identifies hairy cell leukemia as another specific hematologic differential diagnosis that must be separated from mantle cell lymphoma.
treatments:
- name: Ibrutinib
description: >-
First-in-class BTK inhibitor with high activity in relapsed/refractory MCL.
Achieves overall response rates of 65-70%. Also being studied in frontline
combinations. Continuous therapy until progression or intolerance.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: ibrutinib
term:
id: CHEBI:76612
label: ibrutinib
evidence:
- reference: PMID:26059948
reference_title: "Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Ibrutinib, an oral inhibitor of Bruton tyrosine kinase, is approved for patients with mantle cell lymphoma (MCL) who have received one prior therapy."
explanation: This directly supports ibrutinib as an approved treatment for relapsed mantle cell lymphoma.
- reference: PMID:26059948
reference_title: "Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The ORR was 67% (23% complete response), with a median duration of response of 17.5 months."
explanation: This phase 2 trial supports the stated high single-agent activity of ibrutinib in relapsed or refractory mantle cell lymphoma.
- name: Acalabrutinib
description: >-
Second-generation selective BTK inhibitor with efficacy in relapsed MCL
and potentially improved tolerability compared to ibrutinib.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: acalabrutinib
term:
id: CHEBI:167707
label: acalabrutinib
evidence:
- reference: clinicaltrials:NCT02213926
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell Lymphoma (MCL)."
explanation: This phase 2 mantle cell lymphoma trial directly supports acalabrutinib as a disease-relevant therapeutic agent in relapsed or refractory MCL.
- name: Intensive Chemotherapy with ASCT
description: >-
For younger, fit patients, intensive induction regimens (R-DHAP, R-HyperCVAD)
followed by high-dose therapy and autologous stem cell transplant consolidation
achieves prolonged remissions. Standard approach for transplant-eligible patients.
treatment_term:
preferred_term: hematopoietic stem cell transplantation
term:
id: MAXO:0000747
label: hematopoietic stem cell transplantation
evidence:
- reference: PMID:19556426
reference_title: "How I treat mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Very intensive regimens, including autologous and allogeneic stem cell transplantation, seem required to improve the outcome"
explanation: This treatment review supports intensive regimens incorporating stem cell transplantation as an outcome-improving strategy in mantle cell lymphoma.
- name: Bendamustine-Rituximab
description: >-
Effective frontline regimen for older or transplant-ineligible patients.
Achieves high response rates with manageable toxicity.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: bendamustine
term:
id: CHEBI:135515
label: bendamustine
- preferred_term: rituximab
term:
id: NCIT:C1702
label: Rituximab
evidence:
- reference: PMID:26411584
reference_title: "Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "bendamustine-rituximab is an effective therapy with manageable toxicity in relapsed/refractory MCL."
explanation: This phase 2 study directly supports bendamustine plus rituximab as an active mantle cell lymphoma regimen with a high response rate in relapsed or refractory disease.
- reference: clinicaltrials:NCT01415752
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: "PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma."
explanation: This directly supports bendamustine-rituximab as a frontline regimen under formal study in older patients with previously untreated mantle cell lymphoma, although the abstract summary does not report the regimen-specific outcomes.
- name: CAR-T Cell Therapy
description: >-
CD19-directed CAR-T cells (brexucabtagene autoleucel) approved for
relapsed/refractory MCL after BTK inhibitor failure. Achieves durable
remissions in heavily pretreated patients.
treatment_term:
preferred_term: immunotherapy
term:
id: MAXO:0001002
label: immunotherapy procedure
evidence:
- reference: clinicaltrials:NCT02601313
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL)."
explanation: This phase 2 trial directly supports CD19-directed CAR-T therapy as a disease-specific treatment strategy for relapsed or refractory mantle cell lymphoma.
- name: Venetoclax
description: >-
BCL2 inhibitor with activity in relapsed MCL, particularly in combination
with BTK inhibitors. Being evaluated in multiple combination regimens.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: venetoclax
term:
id: CHEBI:133021
label: venetoclax
evidence:
- reference: DOI:10.1002/ajh.25487
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax)."
explanation: This 2019 clinical review supports venetoclax as one of the nonchemotherapeutic agents producing notable responses in mantle cell lymphoma.
- reference: clinicaltrials:NCT03112174
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL."
explanation: This confirms active phase 3 evaluation of venetoclax in rational BTK-inhibitor combination therapy for mantle cell lymphoma.
disease_term:
preferred_term: mantle cell lymphoma
term:
id: MONDO:0018876
label: mantle cell lymphoma
mappings:
mondo_mappings:
- term:
id: MONDO:0018876
label: mantle cell lymphoma
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this mantle cell lymphoma entry.
classifications:
icdo_morphology:
classification_value: Lymphoma
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma"
explanation: This supports classifying mantle cell lymphoma within lymphoma morphology.
harrisons_chapter:
- classification_value: cancer
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma"
explanation: As a malignant B-cell lymphoma, mantle cell lymphoma belongs within the cancer chapter framework.
- classification_value: hematologic malignancy
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma"
explanation: This supports mantle cell lymphoma as a hematologic malignancy.
datasets:
- accession: geo:GSE93291
title: A new molecular assay for the proliferation signature in mantle cell lymphoma applicable to formalin-fixed paraffin-embedded biopsies
description: >-
GEO microarray cohort of mantle cell lymphoma samples used for
coexpression-network analysis, prognostic modeling, and survival
prediction.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
conditions:
- mantle cell lymphoma
platform: GEO
publication: PMID:32219041
evidence:
- reference: PMID:32219041
reference_title: "Identification of key gene modules and hub genes of human mantle cell lymphoma by coexpression network analysis."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: "METHODS: The microarray dataset GSE93291 was downloaded from the Gene Expression Omnibus database."
explanation: This explicitly identifies GSE93291 as a GEO mantle cell lymphoma microarray dataset used for transcriptomic network analysis.
- reference: PMID:35052318
reference_title: "Artificial Intelligence Analysis of Gene Expression Predicted the Overall Survival of Mantle Cell Lymphoma and a Large Pan-Cancer Series."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: "First, we analyzed a series of 123 cases (GSE93291)."
explanation: This independent analysis confirms reuse of GSE93291 as a mantle cell lymphoma gene-expression cohort for survival modeling.
notes: >-
Published reanalyses report 121 to 123 mantle cell lymphoma cases from this
accession, reflecting analysis-specific filtering rather than a difference
in disease context.
clinical_trials:
- name: NCT02213926
phase: PHASE_II
status: ACTIVE_NOT_RECRUITING
description: >-
Open-label phase 2 study evaluating acalabrutinib in relapsed or refractory
mantle cell lymphoma.
evidence:
- reference: clinicaltrials:NCT02213926
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell Lymphoma (MCL)."
explanation: This trial directly studies acalabrutinib in the relevant relapsed or refractory mantle cell lymphoma population.
- name: NCT02601313
phase: PHASE_II
status: COMPLETED
description: >-
Multicenter phase 2 trial evaluating brexucabtagene autoleucel (KTE-X19)
for relapsed or refractory mantle cell lymphoma.
evidence:
- reference: clinicaltrials:NCT02601313
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL)."
explanation: This trial directly supports CAR-T cell therapy as a disease-specific interventional strategy in relapsed or refractory mantle cell lymphoma.
- name: NCT01415752
phase: PHASE_II
status: ACTIVE_NOT_RECRUITING
description: >-
Randomized phase 2 study in patients aged 60 years or older comparing
bendamustine-rituximab-based induction and consolidation strategies in
previously untreated mantle cell lymphoma.
evidence:
- reference: clinicaltrials:NCT01415752
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma."
explanation: This trial directly anchors bendamustine-rituximab-based therapy within the clinical-trial landscape for previously untreated older mantle cell lymphoma patients.
- name: NCT03112174
phase: PHASE_III
status: COMPLETED
description: >-
Multinational randomized phase 3 study comparing ibrutinib plus venetoclax
against ibrutinib plus placebo in mantle cell lymphoma.
evidence:
- reference: clinicaltrials:NCT03112174
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL."
explanation: This trial supports late-phase evaluation of venetoclax-containing combination therapy in mantle cell lymphoma.
references:
- reference: PMID:34114641
title: The pathologic diagnosis of mantle cell lymphoma.
found_in:
- papers.md
findings:
- statement: Pathologic diagnosis of mantle cell lymphoma integrates morphology, immunophenotype, cytogenetics, and molecular profiling.
supporting_text: "This review will focus on the pathologic diagnosis of MCL using the traditional morphological and immunophenotypic strategies combined with cytogenetic characteristics and recently identified molecular profile."
evidence:
- reference: PMID:34114641
reference_title: "The pathologic diagnosis of mantle cell lymphoma."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "This review will focus on the pathologic diagnosis of MCL using the traditional morphological and immunophenotypic strategies combined with cytogenetic characteristics and recently identified molecular profile."
explanation: This finding summarizes the diagnostic integration emphasized in the source review.
- reference: PMID:32584970
title: Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes.
found_in:
- papers.md
findings:
- statement: Mantle cell lymphoma comprises conventional and leukemic non-nodal molecular subtypes with distinct genomic complexity and clinical behavior.
supporting_text: "Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior."
evidence:
- reference: PMID:32584970
reference_title: "Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior."
explanation: This finding captures the subtype framework established by the genomic analysis.
- reference: PMID:16155021
title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
found_in:
- papers.md
findings:
- statement: Dysregulation of cell-cycle control and DNA-damage response pathways is central to mantle cell lymphoma pathogenesis.
supporting_text: "Most of these alterations appear to disturb the cell cycle machinery/interfere with the cellular response to DNA damage, thus making MCL a paradigm for cell cycle and DNA damage response dysregulation in cancer in general."
evidence:
- reference: PMID:16155021
reference_title: "Pathogenesis of mantle-cell lymphoma: all oncogenic roads lead to dysregulation of cell cycle and DNA damage response pathways."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Most of these alterations appear to disturb the cell cycle machinery/interfere with the cellular response to DNA damage, thus making MCL a paradigm for cell cycle and DNA damage response dysregulation in cancer in general."
explanation: This finding restates the mechanistic conclusion from the review.
- reference: PMID:20940415
title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
found_in:
- papers.md
findings:
- statement: PI3K/AKT/mTOR and NF-kB pathway activity contribute to survival and proliferation in mantle cell lymphoma.
supporting_text: "Several signaling pathways contribute to MCL pathogenesis, including the often constitutively activated PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival. WNT, Hedgehog, and NF-κB pathways also appear to be important."
evidence:
- reference: PMID:20940415
reference_title: "Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Several signaling pathways contribute to MCL pathogenesis, including the often constitutively activated PI3K/AKT/mTOR pathway, which promotes tumor proliferation and survival. WNT, Hedgehog, and NF-κB pathways also appear to be important."
explanation: This finding summarizes the key survival-signaling pathways highlighted in the review.
- reference: DOI:10.1182/bloodadvances.2023011763
title: Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: Mantle cell lymphoma (MCL) is an uncommon mature B-cell lymphoma that presents a clinical spectrum ranging from indolent to aggressive disease, with challenges in disease management and prognostication.
supporting_text: Mantle cell lymphoma (MCL) is an uncommon mature B-cell lymphoma that presents a clinical spectrum ranging from indolent to aggressive disease, with challenges in disease management and prognostication.
evidence:
- reference: DOI:10.1182/bloodadvances.2023011763
reference_title: Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma
supports: SUPPORT
evidence_source: OTHER
snippet: Mantle cell lymphoma (MCL) is an uncommon mature B-cell lymphoma that presents a clinical spectrum ranging from indolent to aggressive disease, with challenges in disease management and prognostication.
explanation: Deep research cited this publication as relevant literature for Mantle Cell Lymphoma.
- reference: DOI:10.1200/jco.21.02370
title: Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
supporting_text: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
evidence:
- reference: DOI:10.1200/jco.21.02370
reference_title: Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL).
explanation: Deep research cited this publication as relevant literature for Mantle Cell Lymphoma.
- reference: DOI:10.3389/fimmu.2024.1373269
title: 'Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma'
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: In Mantle Cell Lymphoma (MCL), the role of macrophages within the tumour microenvironment (TME) has recently gained attention due to their impact on prognosis and response to therapy.
supporting_text: In Mantle Cell Lymphoma (MCL), the role of macrophages within the tumour microenvironment (TME) has recently gained attention due to their impact on prognosis and response to therapy.
evidence:
- reference: DOI:10.3389/fimmu.2024.1373269
reference_title: 'Empowering macrophages: the cancer fighters within the tumour microenvironment in mantle cell lymphoma'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: In Mantle Cell Lymphoma (MCL), the role of macrophages within the tumour microenvironment (TME) has recently gained attention due to their impact on prognosis and response to therapy.
explanation: Deep research cited this publication as relevant literature for Mantle Cell Lymphoma.
- reference: DOI:10.3390/cancers17040696
title: Updates on the Biological Heterogeneity of Mantle Cell Lymphoma
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: Advancements in mantle cell lymphoma (MCL) have illuminated the disease’s molecular diversity, leading to a wide variation in the outcomes observed in MCL.
supporting_text: Advancements in mantle cell lymphoma (MCL) have illuminated the disease’s molecular diversity, leading to a wide variation in the outcomes observed in MCL.
evidence:
- reference: DOI:10.3390/cancers17040696
reference_title: Updates on the Biological Heterogeneity of Mantle Cell Lymphoma
supports: SUPPORT
evidence_source: OTHER
snippet: Advancements in mantle cell lymphoma (MCL) have illuminated the disease’s molecular diversity, leading to a wide variation in the outcomes observed in MCL.
explanation: Deep research cited this publication as relevant literature for Mantle Cell Lymphoma.
- reference: DOI:10.3390/hematolrep16010006
title: 'Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study'
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials.
supporting_text: Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials.
evidence:
- reference: DOI:10.3390/hematolrep16010006
reference_title: 'Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials.
explanation: Deep research cited this publication as relevant literature for Mantle Cell Lymphoma.
- reference: DOI:10.46883/2023.25921002
title: Current Treatments in Mantle Cell Lymphoma
found_in:
- Mantle_Cell_Lymphoma-deep-research-falcon.md
findings:
- statement: Current Treatments in Mantle Cell Lymphoma
supporting_text: Current Treatments in Mantle Cell Lymphoma