Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Classic Hodgkin Lymphoma. Core disease mechanisms, molecular and cellular...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 18
• Snippets retrieved: 20

Relevant Papers

[1] P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome

• Authors: Pablo Álvarez-Carrasco, Fernanda Morales-Villamil, C. Maldonado-Bernal
• Year: 2025
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/e5804b5ab8e1ed680a595670111915afd0be21fd
• DOI: 10.3390/ijms26104701
• PMID: 40429842
• PMCID: 12112708
• Citations: 6
• Summary: Recent advances in combating P-gp-mediated resistance are examined, including the development of novel P-gp inhibitors, innovative drug delivery systems, and strategies to modulate P-gp expression or activity, including targeting relevant signaling pathways and exploring drug repurposing.
• Evidence snippets:
• Snippet 1 (score: 0.478) > Lymphomas, a diverse group of blood cancers originating in the lymphatic system, are primarily classified based on the lymphocyte type involved: B-cell, T-cell, or NK-cell. The World Health Organization (WHO) classification is the most widely accepted framework, considering morphology, immunophenotype, genetics, and clinical presentation. B-cell lymphomas, the most common type, include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma [83]. T-cell and NK-cell lymphomas, such as peripheral T-cell lymphomas and anaplastic large-cell lymphoma, are less common and often more aggressive. Hodgkin lymphoma, distinct from non-Hodgkin lymphomas, is characterized by the presence of Reed-Sternberg cells. Previous classification systems, such as the Revised European-American Lymphoma (REAL) classification and the Kiel classification, contributed to the development of the current WHO classification, emphasizing histological and immunophenotypic features [84,85]. > About 30% of diffuse large B-cell lymphoma patients display early relapse and 10% show therapy-refractory disease, often due to the development of multidrug resistance. The mechanisms underlying multidrug resistance in lymphomas are complex and include target gene mutations, metabolic reprogramming, overexpression of drug efflux transporters such as P-gp, upregulation of anti-apoptotic proteins, and enhanced DNA damage repair. P-gp increases resistance to chemotherapy, targeted therapy, and immunotherapy in lymphomas, clinically leading to poor treatment outcomes [86]. > Non-Hodgkin lymphoma (NHL) is a prevalent hematological malignancy arising from lymphoid tissue and lymph nodes throughout the body. Consequently, NHL can manifest in several anatomical locations. Chemotherapy constitutes the primary therapeutic modality for most NHL subtypes [87].

[2] CD20 role in pathophysiology of Hodgkin's disease.

• Authors: Marcelo Antônio Oliveira Santos, M. M. Lima
• Year: 2017
• Venue: Revista da Associacao Medica Brasileira
• URL: https://www.semanticscholar.org/paper/04e73161107ceb5fae03a0e118c8f7dd6c33543c
• DOI: 10.1590/1806-9282.63.09.810
• PMID: 29239464
• Citations: 16
• Summary: CD20 function in Hodgkin's lymphoma development, its influence on disease evolution and outcomes, as well as its effects on therapeutics and patients' prognostic are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.473) > Hodgkin's lymphoma (HL) is a tumor comprising non-malignant and malignant B-cells. Classical HL expresses CD15+ and CD30+ antigens, and 20 to 40% of patients are CD20+. This antigen is a ligand free protein present in B lymphocyte cells and its function is not well known. Some studies suggest that expression of CD20 may play a major role in Hodgkin's disease pathophysiology and may affect the patients' treatment prognosis, as well as relapse and refractory response. In the past few years, development of monoclonal anti-CD20 antibodies changed drastically the treatment for non-Hodgkin lymphomas in which CD20 is expressed. HL treatment is essentially composed of radiotherapy and chemotherapy; however, monoclonal anti-CD20 antibodies applicability is not well delimitated due to lack of information about clinical outcomes with anti-CD20 monotherapy or combined drug therapy using a classic regimen, as well as about CD20 pathophysiology mechanisms in B-cells tumors. The objective of our review is to discuss CD20 function in Hodgkin's lymphoma development, its influence on disease evolution and outcomes, as well as its effects on therapeutics and patients' prognostic.

[3] The Lymphoproliferative Disorders: Handbook of diagnosis, investigation and management

• Authors: G. Morgan, A. Jack, J. Child
• Year: 1998
• Venue: British Journal of Cancer
• URL: https://www.semanticscholar.org/paper/941780a301f63ddd89a00ed9c11aabdf76c2ed33
• DOI: 10.1038/sj.bjc.6690402
• PMCID: 2362316
• Citations: 5
• Summary: Part 1 Principles of diagnosis and treatment: the structure of the lymphoid system laboratory methods for the diagnosis and classification of lymphoproliferative disorders staging and imaging of lymphoarthritis diseases and the development of classifications of lymphanoplastic disorders.
• Evidence snippets:
• Snippet 1 (score: 0.450) > somewhat understated, particularly for Hodgkin's disease, in which, at present, assessment of mediastinal masses on chest X-ray remains a major factor in therapeutic decisions. The role of magnetic resonance imaging as a means of assessing disease viability in residual masses and staging the bone marrow is overstated since there have been conflicting reports of the value of this technique and, unfortunately, the chapter presents relatively little data on the use of Gallium scanning and none on the use of PET scanning, which is an emerging technique in lymphomas. > The chapter on principles of therapy begins with an excellent description of apoptopic pathways and the way in which currently available treatments can modify these. It is a welcome change from the standard account of the action of cytotoxic drugs and radiotherapy etc. > Section 2 of the book covers the specific lymphoproliferative disorders, divided up roughly along the lines of the REAL classification, although the authors acknowledge that it was not possible to adhere strictly to this. Nevertheless, this provides a novel approach to the accounts of these various lymphoma entities. > Each of these chapters take a roughly similar approach to the groups of diseases being discussed. Each provides a thorough description of the diagnosis, pathology and molecular pathology of the disorders followed by, in most cases, a concise but relatively brief account of treatment. This section of the book is particularly strong in its coverage of pathology, diagnosis and underlying molecular mechanisms, and is heavily biased in this direction. Accounts of management of the diseases are relatively brief and will be inadequate for those who wish to gain an insight into some of the complexities of clinical management. For example, the chapter on Hodgkin's disease provides an elegantly written account of the various sub-types of Hodgkin's disease, including lymphocyte predominant nodular Hodgkin's disease and then the various types of classical Hodgkin's with an extensive description of their pathology, the nature of the Reed-Sternberg cell, etc. However, treatment issues in Hodgkin's disease are condensed into only approximately three pages and fail to convey the complexity of the treatment decisions in this disease, the balance between disease control and long-term toxicity and the many ongoing clinical trials. Similarly, in this chapter and

[4] Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets

• Authors: E. Mata, A. Díaz-López, A. M. Martín-Moreno, M. Sánchez-Beato, I. Varela et al.
• Year: 2017
• Venue: Oncotarget
• URL: https://www.semanticscholar.org/paper/024bfd902d2428c06820bdedab50ba27b3a5f313
• DOI: 10.18632/oncotarget.22799
• PMID: 29340061
• PMCID: 5762329
• Citations: 37
• Influential citations: 3
• Summary: The mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg cells, is described, confirming the presence of strong genomic heterogeneity and indicating new pathogenic mechanisms and therapeutic opportunities in this disease.
• Evidence snippets:
• Snippet 1 (score: 0.446) > Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors in vitro constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease.

[5] Recurrent Composite Lymphoma in an Elderly Man: A Case of Marginal Zone Lymphoma With Classic Hodgkin Features Treated With Brentuximab and Immunotherapy

• Authors: Muhammad Daniyal, Anamm Polani, Amrat Kumar, Ahmad Raja, Marcy Canary
• Year: 2025
• Venue: Cureus
• URL: https://www.semanticscholar.org/paper/f0b4e77a96f22f5b65eb81cb5e0190f1d845dcfd
• DOI: 10.7759/cureus.84943
• PMID: 40585708
• PMCID: 12203287
• Summary: The case of an 82-year-old man with a history of low-grade B-cell lymphoma, now presenting with recurrent disease characterized by a composite histology of marginal zone lymphoma (MZL) and classic Hodgkin's lymphoma (CHL), illustrates key considerations in the diagnosis, staging, and treatment of CLs in geriatric patients.
• Evidence snippets:
• Snippet 1 (score: 0.440) > Composite lymphoma (CL) is a rare hematologic condition characterized by the coexistence of two or more distinct lymphoma types within the same anatomical location or biopsy specimen. Although it comprises only 1%-4% of all lymphomas, its clinical importance lies in its diagnostic complexity and implications for treatment selection and prognosis [1]. The most frequently reported combination involves a B-cell non-Hodgkin's lymphoma (NHL), such as marginal zone lymphoma (MZL) or follicular lymphoma, paired with classic Hodgkin's lymphoma (CHL), as seen in this case [2]. > The etiology and pathogenesis of CL remain incompletely understood, though several theories have been proposed. These include the possibility of biclonal or divergent clonal evolution from a common progenitor, genetic instability, prior immunosuppressive therapy, and viral involvement, particularly Epstein-Barr virus (EBV) in the Hodgkin component [3,4]. EBV is known to contribute to lymphomagenesis by promoting B-cell proliferation and survival, especially in immunosenescent or immunocompromised hosts, a relevant consideration in elderly patients [5]. > From a diagnostic standpoint, CLs challenge conventional classification schemes. They often require extensive immunohistochemical analysis and molecular studies to distinguish and characterize each component. Immunophenotypic markers such as CD20, CD30, CD15, PAX5, Bcl-2, and CD3, in conjunction with EBV-encoded RNA (EBER) in situ hybridization, play a critical role in differentiating the B-cell and Hodgkin components [6]. Misdiagnosis or underdiagnosis can lead to suboptimal therapeutic strategies, particularly if only the indolent or aggressive component is identified. > Clinically, patients may present with B-symptoms, lymphadenopathy, or findings on surveillance imaging, as in our case. Management strategies for CL are not standardized due to its rarity and heterogeneity.
• Snippet 2 (score: 0.424) > Composite lymphoma (CL) is a rare and diagnostically challenging condition where two or more distinct types of lymphoma coexist within the same anatomical site. We report the case of an 82-year-old man with a history of low-grade B-cell lymphoma, now presenting with recurrent disease characterized by a composite histology of marginal zone lymphoma (MZL) and classic Hodgkin's lymphoma (CHL). Management involved single-agent brentuximab due to comorbidities, followed by immune checkpoint inhibition upon relapse. This case illustrates key considerations in the diagnosis, staging, and treatment of CLs in geriatric patients. The clinical course further highlights the importance of personalized therapy selection based on age, comorbidities, and histological features. This case also contributes to the limited literature on real-world outcomes in patients with CL and underscores the need for future prospective studies and biomarker-driven treatment approaches in this rare entity.

[6] Current Progress in Investigating Mature T- and NK-Cell Lymphoma Gene Aberrations by Next-Generation Sequencing (NGS)

• Authors: Lifen Zhu, Shufang Xie, Chen Yang, Nanni Hua, Yi Wu et al.
• Year: 2021
• Venue: Cancer Management and Research
• URL: https://www.semanticscholar.org/paper/803d9d0d479883b6ac9fba1df46d9ee919821dd9
• DOI: 10.2147/CMAR.S299505
• PMID: 34239326
• PMCID: 8259727
• Citations: 3
• Summary: Advances in NKTCL-related gene mutations are reviewed and next-generation sequencing is an increasingly developing gene detection technique, which has been widely used in lymphoma genetic research in recent years, making genetic mutation a new research hotspot in lymph cancer.
• Evidence snippets:
• Snippet 1 (score: 0.438) > Hodgkin's lymphoma is divided into nodular lymphocytes and classic Hodgkin's lymphoma, the former being the dominant type of the disease. 17 NK/T extranodal cell lymphoma is a major NK cell lymphoma with a ratio of 10.4% in mature T cell lymphoma and NK cell lymphoma. 18 Similar to other malignant proliferative diseases, lymphoma has genetic instability and chromosomal abnormalities, which together directly cause the development of malignancy. > NGS has been applied to accurate diagnosis of gene mutation, analysis of pathogenesis, prognosis monitoring and so on. 19 Recent developments in lymphoma genome sequencing have led to a preliminary appreciation of somatic mutation complexity in these tumors as well as a number of findings of significant functional and clinical significance, including studies on the prognostic impact of some genes on lymphoma or potential as drug targets. 20 ompared with cases of B cell lymphoma, there has been slower use of NGS for molecular studies in mature NK/ T-cell lymphoma. 21 This article reviews the application of NGS in scientific analysis and clinical detection of mature T-and NK-cell lymphoma (

[7] Editorial: Pathogenesis, immune escape, prognosis, and novel management of lymphoid proliferative disorders

• Authors: W. Sang
• Year: 2022
• Venue: Frontiers in Immunology
• URL: https://www.semanticscholar.org/paper/f34f83a45e0eca9c766112ae4fc2ef2775b0a177
• DOI: 10.3389/fimmu.2022.1063418
• PMID: 36479113
• PMCID: 9720891
• Summary: This Research Topic examines lymphoproliferative diseases (LPD), focusing on the pathological microenvironment, immune escape, prognosis, and the processes involved with seeking novel treatment methods. Including four editors who worked with invited reviewers, for this collection we invited potential contributors and accepted online contributions. Based on the comprehensive evaluation of the theme fi t and the quality of those manuscripts, 17 contributions were accepted. These manuscripts incl...
• Evidence snippets:
• Snippet 1 (score: 0.425) > This Research Topic examines lymphoproliferative diseases (LPD), focusing on the pathological microenvironment, immune escape, prognosis, and the processes involved with seeking novel treatment methods. Including four editors who worked with invited reviewers, for this collection we invited potential contributors and accepted online contributions. Based on the comprehensive evaluation of the theme fi t and the quality of those manuscripts, 17 contributions were accepted. These manuscripts include different types of LPD, such as hemophagocytic lymphohistiocytosis (HLH), follicular cell lymphoma (FL), peripheral T cell lymphoma (PTCL), diffuse large B cell lymphoma (DLBCL), Castleman disease (CD), extranodal natural killer/T cell lymphoma (NK/ Hodgkin lymphoma (HL), and other subtypes of non-Hodgkin lymphoma (NHL). LPDs are often driven by different causes and have great differences in pathogenesis, pathology, and genetic characteristics. Clarifying these potential cloning and transformation mechanisms and regulatory mechanisms us better understand these kinds of diseases. The prognosis of DLBCL in the is et al. the elderly DLBCL is accompanied by undesirable clinical and molecular features, represented by the accumulation of oncogenic mutations and with the MYD88-like genetic subtype and immunosuppressive tumor microenvironment alterations. It is proposed that, in the elderly DLBCL patients need to explore new treatment methods based on these characteristics. Tumor protein 53 ( TP53 ) mutation predicts an

[8] Expression of Apoptosis Related and Proliferative Proteins in Malignant Lympho-Proliferative Disorders

• Authors: Z. Jairajpuri, Rekha Ghai, S. Saluja, S. Kapur, K. Bhowmik
• Year: 2017
• Venue: Iranian Journal of Pathology
• URL: https://www.semanticscholar.org/paper/0789eaebc75bc50bdeeab42c1e2171cd9832575d
• DOI: 10.30699/IJP.2017.25051
• PMID: 29531548
• PMCID: 5835371
• Citations: 3
• Summary: An immunohistochemical analysis of patterns of apoptotic and cell proliferative related protein expression in different histological grades and immune phenotypes of malignant lymphomas and other lymphoproliferative disorders indicated the important role of Bcl-2 and Bax in biological behavior of lymphomas.
• Evidence snippets:
• Snippet 1 (score: 0.423) > The histological spectrum of benign and malignant lymphoproliferative disorders range from non-specific reactive hyperplasia to atypical lymphoid hyperplasia and lymphomas (Non-Hodgkin's Lymphoma (NHL) and Hodgkin's Disease (HD) (1). Molecular, biological and genetic discoveries have improved the primary diagnosis of lymphoproliferative processes permitting better assessment of prognosis within histologic groups (2). Furthermore, integration of clinical features with recent advances in lymphoma biology has contributed significantly to the understanding of tumor specific variables that have a direct impact on clinical behaviors. Integration of clinical features with morphology, cytochemistry and immune phenotype has clinical and prognostic value (3).A key issue regarding lymphoid neoplasm is to discriminate between disease entities and prognostic factors. Both apoptosis and mitosis serve as potential prognostic indicators and are firmly interrelated. The growth of both indolent and aggressive lymphomas depends on the proliferation and death rates of cancer cells. Cell proliferation, as determined by immunocytochemistry, using proliferation antigens Ki-67 and Proliferating Cell Nuclear Antigen (PCNA), is the principal determinant of tumor progression and prognosis. Apoptosis or programmed cell death on the other hand, occurs through a sequence of active mechanisms within the cell that are controlled by positive and negative regulators of the apoptotic pathway (4). A number of genes including c-myc, P53, Bcl-2 and Bax are known to regulate the apoptotic pathway with some preventing and others promoting cell death. The failure of apoptosis leads to the development of many tumors and often renders them resistant to cytotoxic therapies. In hematologic malignancies, this impairment of apoptosis is often caused by overexpression of the pro-survival protein Bcl-2. Abnormally high levels of Bcl-2 help sustain tumors and can be used as a target in an approach to treat various hematologic malignancies (5).

[9] Role of CREB Protein Family Members in Human Haematological Malignancies

• Authors: F. D'Auria, R. Pietro
• Year: 2013
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/efe976ba9ae3c96fddd2df18a8ea4b90dd16aa8a
• DOI: 10.5772/55368
• Citations: 9
• Influential citations: 1
• Summary: The present chapter is aimed at revising literature focusing on the involvement of CREB/ATF family members in leukemogenesis and lymphomagenesis, in order to gain more insight into this matter that could result useful to the treatment of leukaemia and lymphoma diseases.
• Evidence snippets:
• Snippet 1 (score: 0.420) > Lymphomas are haematological malignancies of the lymphoid system. Deregulated gene expression is a hallmark of cancer and is well documented in B-cell lymphomas [98]. B cells are particularly susceptible to malignant transformation since the mechanisms involved in antibody diversification can cause chromosomal translocations and oncogenic mutations. Bcell lymphomas include Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (B-NHL). B-NHL consists of a heterogeneous group of diseases whose pathogenesis is associated with multiple genetic lesions affecting oncogenes and tumour-suppressor genes and whose treatment is related to the different grade of malignancy. The most common type of B-NHL is represented by the diffuse large B-cell lymphoma (DLBCL), which generally arises as a clinical evolution of the follicular lymphoma (FL). A number of papers have demonstrated the involvement of CREB family members in the pathogenesis of lymphoma. It has been previously found that CREB acts as a positive regulator of the translocated BCL-2 allele in FLs with the t(14;18) translocation [60] and that the high constitutive expression of ATF-3 is linked to the viability of Hodgkin/Reed-Sternberg cells and, thus, considered as a molecular hallmark of classical HL [99]. More recently, a number of studies have disclosed the implication of the HAT proteins CBP and p300 as tumour suppressors in B-cell neoplasms [100-102]. Nevertheless, the various mechanisms through which each of these cofactors specifically contributes to lymphomagenesis are still to be elucidated. As before mentioned, CBP and p300 function as co-activators of transcription factors and acetylate proteins relevant to lymphomagenesis such as p53, NF-κB, Bcl-6 and Hsp90 [100, 103,104].

[10] Identification of ATP1B1, a key copy number driver gene in diffuse large B-cell lymphoma and potential target for drugs

• Authors: Shuo Zhang, Hongmin Wang, Aichun Liu
• Year: 2022
• Venue: Annals of Translational Medicine
• URL: https://www.semanticscholar.org/paper/a38e9a2ada49df4b57db652d8b663c64939bdde1
• DOI: 10.21037/atm-22-4709
• PMID: 36388804
• PMCID: 9652577
• Citations: 5
• Summary: A Kyoto Encyclopedia of Genes and Genomes analysis found that ATP1B1 is a copy number driver gene that could potentially be adopted as a diagnostic biomarker and therapeutic target of DLBCL.
• Evidence snippets:
• Snippet 1 (score: 0.417) > Lymphoma is a malignant tumor that originates from the lymphoid hematopoietic system. Hodgkin's and non-Hodgkin's lymphomas are two common types. Existing data surveys have estimated that in 2020, there were 509,590 new cases as well as more than 248,724 lymphoma deaths worldwide (1). Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for approximately 30% of all cases, which also includes specific subtypes or disease entities (2). Among the current clinical diagnostic and therapeutic strategies, R-CHOP (retuximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is the preferred treatment choice and has an excellent ability to inhibit disease development (3). There are many patients who either relapse or experience primary refractory disease and eventually succumb to the illness (4,5). To provide new diagnostic and therapeutic ideas for the detection and treatments of DLBCL, DLBCL biomarker-related research and further exploration of the related molecular mechanisms are in demand. Thus, our research provides a new diagnostic and treatment strategy for the clinical treatment of DLBCL. > Genetic elements are key to DLBCL's etiology. Meanwhile, the development and progression of DLBCL are derived from a multistep pathway that involves genetic alteration accumulations at proto-oncogenes and carcinogenesis of tumor suppressive genes. The mechanisms of the above-mentioned process include chromosomal alterations, single nucleotide variants, copy number variations (CNVs), and epigenetic alterations (6,7). DLBCL carcinogenetic abnormality detection may act as a key indicator of prognosis, and could also act as a key contributing factor to the customized treatment of special markers. > CNVs are a recognized cancer hallmark that may result in the activation of oncogenes and the inactivation of genes that express tumor-suppressing attributes in several malignancies.

[11] Classic Hodgkin Lymphoma - Old Disease, New Directions: An Update on Pathology, Molecular Features and Biological Prognostic Markers.

• Authors: Anamarija M. Perry, Lauren B. Smith, A. Bagg
• Year: 2021
• Venue: Acta medica academica
• URL: https://www.semanticscholar.org/paper/02e166d06164db4291a94b6778ec1c744614cc97
• DOI: 10.5644/ama2006-124.329
• PMID: 34075767
• Citations: 7
• Summary: The aim of this paper is to review morphologic, immunophenotypic, and molecular features of classic Hodgkin lymphoma, as well as different prognostic markers in this neoplasm. Classic Hodgkin lymphoma (CHL) accounts for 15-25% of all lymphomas in the Western world. The hallmark of this disease is the neoplastic Hodgkin/Reed-Sternberg (HRS) cell, which is favored to be derived from germinal center B-cells but has lost many of the B-cell markers. HRS cells are scattered within a dense inflammat...
• Evidence snippets:
• Snippet 1 (score: 0.415) > The aim of this paper is to review morphologic, immunophenotypic, and molecular features of classic Hodgkin lymphoma, as well as different prognostic markers in this neoplasm. Classic Hodgkin lymphoma (CHL) accounts for 15-25% of all lymphomas in the Western world. The hallmark of this disease is the neoplastic Hodgkin/Reed-Sternberg (HRS) cell, which is favored to be derived from germinal center B-cells but has lost many of the B-cell markers. HRS cells are scattered within a dense inflammatory infiltrate, and through a network of cytokines and chemokines they shape their microenvironment, evade immune response, survive, and grow. In the last two decades multiple prognostic markers related to HRS cells, the microenvironment or both, have been evaluated in patients with CHL. They include clinical, immunohistochemical, cytogenetic, and molecular markers that can predict survival and identify high-risk patients who will likely relapse after therapy. More recently, circulating tumor DNA analysis by next-generation sequencing has opened new avenues for diagnosis and disease monitoring after therapy. The increased understanding of molecular mechanisms underlying CHL pathogenesis has led to successful implementation of novel therapies, such as anti-PD-1 antibodies, which are becoming a mainstay of treatment in relapsed/refractory patients. CONCLUSION: Currently, pathologic prognostic markers are not routinely assessed at initial diagnosis of CHL. However, as more therapies become available, it will be important to identify patients with high-risk disease who may benefit from more intense or targeted therapy upfront.
• Snippet 2 (score: 0.412) > Hodgkin lymphoma is a common lymphoma in the Western world accounting for 15-25% of all lymphomas. This group is comprised of two morphologically and immunophenotypically distinct entities -classic Hodgkin lymphoma (CHL) which accounts for over 90% of cases and nodular lymphocyte predominant Hodgkin lymphoma (1,2). Although "Hodgkin's disease" was first reported nearly 200 years ago and Hodgkin/Reed-Sternberg (HRS) cells were described at the turn of the 20 th century, the nature of this disease (i.e. neoplastic vs. infectious/inflammatory) remained a mystery for a long time (3,4). The B-cell origin of HRS cells was finally elucidated in the 1990s and the new terminology "Hodgkin lymphoma" was included in the Revised European American Lymphoma (REAL) Classification (5)(6)(7). Since then, CHL has been a focus of extensive research which paved the way for better risk stratification and novel therapies. > Classic Hodgkin lymphoma has a bimodal age distribution, with the first peak from 15 to 35 years of and the second after 55 years of age. In resourcepoor countries, however, the first peak occurs earlier in childhood. The overall male-to-female ratio is 1.5:1, but females have higher incidence of nodular sclerosis subtype of CHL (2,(8)(9)(10). Clini-Clinical Science cally, CHL mainly involves lymph nodes, most frequently above the diaphragm with cervical, mediastinal, axillary, and supraclavicular lymph node chains being most commonly affected. In a subset of patients, extranodal tissues are involved, such as spleen, lungs and liver (2,10). Bone marrow involvement is uncommon, occurring in approximately 5% of patients and is more common in the elderly and HIV positive patients (11).

[12] Impact of Nutritional Status on Survival and Development of Hodgkin’s Lymphoma: A Scoping Review

• Authors: Sabina Krupa-Nurcek, Dominika Wiśniewska, Michał Klimas, Martyna Winiarska, Dominik Jucha et al.
• Year: 2025
• Venue: Nutrients
• URL: https://www.semanticscholar.org/paper/358d0e6ac1fce5128bfe647a150a0c3fed5aedb8
• DOI: 10.3390/nu17233777
• PMID: 41374067
• PMCID: 12694317
• Summary: Available data suggest that a diet rich in vegetables, fruits, fiber, and omega-3 fatty acids may have a protective effect, reducing the risk of developing Hodgkin’s lymphoma and improving prognosis and survival through anti-inflammatory and immune-supporting effects.
• Evidence snippets:
• Snippet 1 (score: 0.409) > The review work indicates that nutrition plays a significant role in both the risk of development and the course and mortality of Hodgkin lymphoma. Excessive consumption of saturated fats, simple sugars and processed meat products can promote cancer transformation by inducing chronic inflammation, immune disorders and oxidative stress. On the other hand, a diet rich in vegetables, fruits, fiber and omega-3 fatty acids has antiinflammatory and immunomodulatory effects, supporting the body's defense mechanisms and improving treatment tolerance. The patient's nutritional status, both before diagnosis and during therapy, affects the prognosis, and malnutrition or obesity may increase the risk of complications and death. Further clinical studies are needed to precisely determine the relationship between diet quality and treatment outcomes in HL. > Nutrition plays a significant role in the course of cancer, including Hodgkin's lymphoma, influencing both disease progression, treatment efficacy, and patient mortality. The mechanisms linking nutritional factors to cancer are extremely complex and involve metabolic, immunological, and epigenetic interactions. Diet can modulate the risk of disease, the course of therapy, and prognosis, and its importance stems from its impact on the immune system, gut microbiota, cellular metabolism, and inflammatory processes. At the molecular level, dietary components influence the proliferation and apoptosis of lymphocytes, from which Hodgkin's lymphoma originates. Excessive intake of saturated fats and simple sugars promotes chronic inflammation and insulin resistance, which can stimulate signaling pathways associated with cancer development. In turn, a diet rich in antioxidants, fiber, and omega-3 fatty acids supports DNA repair mechanisms, reduces oxidative stress, and modulates the immune response, potentially reducing the risk of disease progression. The gut microbiota, shaped by diet, influences immunomodulatory metabolites, which can either support or weaken the effectiveness of chemotherapy. Diet is particularly important during Hodgkin lymphoma treatment. Chemotherapy and radiotherapy lead to taste disturbances, loss of appetite, nausea, and diarrhea, which increase the risk of malnutrition.

[13] Identifying a Novel BCL2L1-Targeting Peptide from Porcine Placenta for Lymphoma Therapy

• Authors: Tassanee Ongtanasup, Nattawan Suwannakul, Komgrit Eawsakul
• Year: 2025
• Venue: ACS Omega
• URL: https://www.semanticscholar.org/paper/bfea8ba76173cceedfd0cc34c31cf55906354dca
• DOI: 10.1021/acsomega.5c09730
• PMID: 41487244
• PMCID: 12756794
• Summary: By balancing high target efficacy with crucial drug-like properties, QPLLLDDR is identified not merely as a candidate but as the most pragmatically viable lead compound for future experimental validation as a parenteral therapeutic for lymphoma.
• Evidence snippets:
• Snippet 1 (score: 0.408) > In the United States, the lifetime risk of developing lymphoma is approximately 2.1%, with a slightly higher prevalence in males (5.0%) compared to females (1.5%). 9 At the molecular level, lymphoma's pathogenesis is characterized by profound genetic and molecular dysregulations involving critical genes such as BCL2L1, 10 CASP3, 11 NFKB1, 12 and Sphingosine-1-phosphate receptors. 13 These molecular players orchestrate intricate cellular processes of survival, proliferation, and apoptosis. The BCL2L1 gene, encoding the BCL-XL protein, serves as a pivotal antiapoptotic regulator, frequently overexpressed in lymphoid neoplasms. Epidemiological studies suggest that genetic alterations in this gene are present in approximately 30−40% of Non-Hodgkin Lymphoma cases, 14 significantly impacting disease progression and treatment outcomes. CASP3, a key executioner caspase, plays a fundamental role in the apoptotic cascade, with its dysregulation potentially contributing to lymphoma progression. Molecular epidemiology research indicates that mutations in this gene are associated with increased treatment resistance and poorer prognosis. 15 NFKB1, a critical transcription factor, emerges as a central mediator of inflammatory responses and cellular survival mechanisms. Epidemiological data suggest that its dysregulation is observed in up to 28−55% of lymphoma cases, 16 correlating with more aggressive disease phenotypes. Sphingosine-1-phosphate receptors facilitate complex signaling pathways that modulate lymphoma cell migration, proliferation, and metastatic potential. Recent studies have highlighted their role in approximately 54.2% of lymphoma cases, presenting potential therapeutic targets. 17 his study uses a systematic method to explore the molecular mechanisms of porcine peptides. Network pharmacology 18 and molecular docking, 19 two methods that can help bridge the gap in our knowledge, were applied. A system approach based on systems biology, network pharmacology can explore the complex interactions between peptides and various related proteins by revealing how peptides affect multiple targets within biological networks.

[14] Genomic landscape of mature B-cell non-Hodgkin lymphomas - an appraisal from lymphomagenesis to drug resistance.

• Authors: D. Panda, N. Das, D. Thakral, Ritu Gupta
• Year: 2022
• Venue: Journal of the Egyptian National Cancer Institute
• URL: https://www.semanticscholar.org/paper/8b2406b177783cfeed38c417e550521d4d2e6ef2
• DOI: 10.1186/s43046-022-00154-z
• PMID: 36504392
• Citations: 4
• Summary: The wide range of genetic aberrancies associated with tumorigenesis, immune escape, and chemoresistance in major B-cell non-Hodgkin lymphomas are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.408) > BACKGROUND > Mature B-cell non-Hodgkin lymphomas are one of the most common hematological malignancies with a divergent clinical presentation, phenotype, and course of disease regulated by underlying genetic mechanism. > MAIN BODY > Genetic and molecular alterations are not only critical for lymphomagenesis but also largely responsible for differing therapeutic response in these neoplasms. In recent years, advanced molecular tools have provided a deeper understanding regarding these oncogenic drives for predicting progression as well as refractory behavior in these diseases. The prognostic models based on gene expression profiling have also been proved effective in various clinical scenarios. However, considerable overlap does exist between the genotypes of individual lymphomas and at the same time where additional molecular lesions may be associated with each entity apart from the key genetic event. Therefore, genomics is one of the cornerstones in the multimodality approach essential for classification and risk stratification of B-cell non-Hodgkin lymphomas. > CONCLUSION > We hereby in this review discuss the wide range of genetic aberrancies associated with tumorigenesis, immune escape, and chemoresistance in major B-cell non-Hodgkin lymphomas.

[15] Predictive Modeling of Drug Response in Non-Hodgkin’s Lymphoma

• Authors: H. Frieboes, B. Smith, Zhihui Wang, M. Kotsuma, Ken Ito et al.
• Year: 2015
• Venue: PLoS ONE
• URL: https://www.semanticscholar.org/paper/391dbd7ad2a4c83c60e034a2d6e0935f040c0e26
• DOI: 10.1371/journal.pone.0129433
• PMID: 26061425
• PMCID: 4464754
• Citations: 23
• Summary: A proof-of-principle for predictive quantification of lymphoma drug therapy was established based on both cellular and tissue-scale physiological contributions, and tissue blood volume fraction was determined to be the most sensitive model parameter and a primary contributor to drug resistance.
• Evidence snippets:
• Snippet 1 (score: 0.404) > Lymphoma drug response has predominantly been studied at the subcellular-to-cellular scale (molecular cancer biology), or at the whole-organ and/or systemic scale (oncology and clinical applications) (e.g., see recent studies [1][2][3][4][5]). Despite a multitude of genetic, proteomic, and histological analyses to understand lymphoma progression and treatment, drug resistance remains a major challenge to chemotherapy [6]. It is well known that specific phenomena at various physical scales contribute to this resistance. At the molecular scale, genetic/proteomic make-up can lead to intrinsic cellular drug resistance [7]; at an intermediate scale, transport barriers in the tissue microenvironment due to diffusion gradients of oxygen, nutrients, and drug may impede optimal response to cell-cycle specific drugs through cell quiescence as well as insufficient drug levels to achieve cytotoxicity [8,9]; at the tissue scale, tumor morphological instability as a result of vascularization irregularities may lead to tumor tissue fragmentation and increased invasiveness [10]. > The relative contribution to drug resistance due to intrinsic cellular mechanisms vs. physiologic resistance originating from the 3D tumor microenvironment is unclear. Cellular-intrinsic drug resistance depends on molecular mechanisms that support individual cell survival, including increased repair pathways and detoxification, adaptations leading to failure of apoptosis, and alterations in transmembrane drug transport [11]. These mechanisms define the resistant phenotype at the molecular scale primarily based on the cells' molecular and genetic properties. Physiologic resistance that is not a direct result of the molecular phenotype can arise when a cell enters a quiescent proliferative state, thus becoming insensitive to the mode of action of cell-cycle specific drugs such as doxorubicin (Dox) and cyclophosphamide. An arrested proliferative state is a well-studied mechanism of physiological resistance to most chemotherapeutic agents currently in use. This resistance may depend on tumor and vascular geometry as well as distance to blood vessels and diffusion and pressure gradients.

[16] BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma

• Authors: Yanfang Wang, Zhen-Hao Zhang, Lian-yong Xi, Hua Wang, Fei Dong
• Year: 2025
• Venue: Discover Oncology
• URL: https://www.semanticscholar.org/paper/fc004bda08760e875c9fbf2cd0f7348dd3aeb9ae
• DOI: 10.1007/s12672-025-02519-x
• PMID: 40327257
• PMCID: 12055718
• Citations: 1
• Summary: Elevated BEND4 levels were linked to poor prognosis and chemoresistance in DLBCL, potentially due to transcriptional regulation and immune suppression roles, and may represent a viable therapeutic target in DLBCL.
• Evidence snippets:
• Snippet 1 (score: 0.403) > Diffuse large B-cell lymphoma (DLBCL) is the most prevalent lymphocytic cancer in adults, comprising 30-40% of non-Hodgkin's lymphoma cases [1]. DLBCL shows substantial variability in clinical presentations, biological traits, and treatment responses [2]. While rituximab-based chemotherapy cures many patients, 40% experience relapse or initial drug resistance [3]. Advances in gene sequencing have classified DLBCL into seven genetic subtypes, each with distinct prognoses and potential targeted treatments [4]. However, the exact mechanisms of tumor recurrence or progression remain unclear, highlighting the need for identifying high-risk biomarkers to improve molecular understanding, enhance risk stratification, and support targeted drug development.

[17] Novel Approaches in Molecular Characterization of Classical Hodgkin Lymphoma

• Authors: Diede A G van Bladel, W. Stevens, M. van den Brand, L. Kroeze, P. Groenen et al.
• Year: 2022
• Venue: Cancers
• URL: https://www.semanticscholar.org/paper/83b26089091ab6fe6ca9ffe9413761b325018d53
• DOI: 10.3390/cancers14133222
• PMID: 35805000
• PMCID: 9264882
• Citations: 11
• Summary: This review provides an overview of the recent advances in genotyping the clonal and mutational landscape of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.
• Evidence snippets:
• Snippet 1 (score: 0.397) > Simple Summary The unique tumor composition of classical Hodgkin lymphoma (cHL), with only a small fraction of malignant Hodgkin and Reed–Sternberg cells within the tumor tissue, has created many challenges to characterize the genetic alterations that drive this lymphoid malignancy. Major advances in sequencing technologies and detailed analysis of circulating tumor DNA in blood samples of patients have provided important contributions to enhance our understanding of the pathogenesis of cHL. In this review, we provide an overview of the recent advances in genotyping the clonal and mutational landscape of cHL. In addition, we discuss different next-generation sequencing applications to characterize tumor tissue and cell-free DNA, which are now available to improve the diagnosis of cHL, and to monitor therapeutic response or disease progression during treatment and follow up of cHL patients. Abstract Classical Hodgkin lymphoma (cHL) represents a B-cell lymphoproliferative disease characterized by clonal immunoglobulin gene rearrangements and recurrent genomic aberrations in the Hodgkin Reed–Sternberg cells in a reactive inflammatory background. Several methods are available for the molecular analysis of cHL on both tissue and cell-free DNA isolated from blood, which can provide detailed information regarding the clonal composition and genetic alterations that drive lymphoma pathogenesis. Clonality testing involving the detection of immunoglobulin and T cell receptor gene rearrangements, together with mutation analysis, represent valuable tools for cHL diagnostics, especially for patients with an atypical histological or clinical presentation reminiscent of a reactive lesion or another lymphoma subtype. In addition, clonality assessment may establish the clonal relationship of composite or subsequent lymphoma presentations within one patient. During the last few decades, more insight has been obtained on the molecular mechanisms that drive cHL development, including recurrently affected signaling pathways (e.g., NF-κB and JAK/STAT) and immune evasion. We provide an overview of the different approaches to characterize the molecular composition of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.

[18] In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

• Authors: C. Aya-Bonilla, E. Camilleri, L. Haupt, R. Lea, M. Gandhi et al.
• Year: 2014
• Venue: BMC Genomics
• URL: https://www.semanticscholar.org/paper/42b9cff292bb57fa69db22d2b49a7433821e8d4b
• DOI: 10.1186/1471-2164-15-390
• PMID: 24885312
• PMCID: 4041994
• Citations: 8
• Influential citations: 1
• Summary: The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.
• Evidence snippets:
• Snippet 1 (score: 0.395) > The identification of altered pathways in tumour cells has provided a more holistic understanding of the pathogenic mechanisms that underlie the genesis, progression and chemoresponse of cancer. As a consequence, malfunction of a gene or a group of genes must be analysed as part of a complex network of components that are highly related to each other. However, this analysis is limited by factors such as the lack of analytic tools to convert and integrate, in a feasible and reliable manner, large amounts of data derived from different high-throughput genomic approaches into outputs with more biological meaning. > Non-Hodgkin's lymphoma (NHL) represents a highly biological and clinical heterogeneous group of blood cancers [1,2]. Two of the most common NHL subtypes are Diffuse Large B-cell Lymphoma (DLBCL), an aggressive lymphoma, and Follicular lymphoma (FL), a slow-growing type of lymphoma, which account for around 50% of NHL cases [1,3]. The poor treatment outcomes obtained between 20-40% of cases with these NHL lymphomas has prompted studies aimed at the discovery of genes and pathways that could act as novel targets for a therapy that increase the survival rates of patients suffering from NHL [4][5][6]. However, the high genetic variability observed within NHL subtypes, has limited the understanding of the pathology of these NHL subtypes, as well as the discovery of new molecular targets for therapeutic development. > In a previous study, the integration of copy number (CNV) and gene expression profiling (GEP) data from DLBCL and FL cases, allowed us to identify common and disease-specific genetic alterations targeting known oncogenic pathways, such as the mitogen activated protein kinase (MAPK) and apoptosis signalling pathways, unmasking common pathogenic mechanisms underlying the malignant phenotype of these biologically and genetically distinct NHL subtypes [7].

Notes

• This provider combines search_papers_by_relevance with snippet_search.
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