Acute lymphoblastic leukemia (ALL) is a malignancy of immature B- or T-lymphoid precursors (lymphoblasts) that proliferate uncontrollably in the bone marrow, blood, and extramedullary sites. It is the most common childhood cancer and the leading cause of cancer-related death in children. Pathogenesis involves acquisition of recurrent genetic lesions (translocations, aneuploidy, gene fusions, and cooperating mutations) that produce a developmental block in lymphoid maturation, driving clonal expansion of blasts and replacement of normal hematopoiesis with consequent marrow failure. Subtypes are defined by lineage (B-ALL versus T-ALL) and by recurrent molecular drivers (e.g., ETV6-RUNX1, TCF3-PBX1, KMT2A rearrangements, BCR-ABL1 / Philadelphia chromosome). Risk stratification, treatment intensity, and prognosis are largely determined by these molecular subtypes.
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name: Acute Lymphoblastic Leukemia
creation_date: '2026-05-08T12:00:00Z'
updated_date: '2026-05-08T13:00:00Z'
description: >-
Acute lymphoblastic leukemia (ALL) is a malignancy of immature B- or T-lymphoid
precursors (lymphoblasts) that proliferate uncontrollably in the bone marrow,
blood, and extramedullary sites. It is the most common childhood cancer and the
leading cause of cancer-related death in children. Pathogenesis involves
acquisition of recurrent genetic lesions (translocations, aneuploidy, gene
fusions, and cooperating mutations) that produce a developmental block in
lymphoid maturation, driving clonal expansion of blasts and replacement of
normal hematopoiesis with consequent marrow failure. Subtypes are defined by
lineage (B-ALL versus T-ALL) and by recurrent molecular drivers (e.g.,
ETV6-RUNX1, TCF3-PBX1, KMT2A rearrangements, BCR-ABL1 / Philadelphia
chromosome). Risk stratification, treatment intensity, and prognosis are
largely determined by these molecular subtypes.
categories:
- Hematologic Malignancy
- Acute Leukemia
- Pediatric Cancer
parents:
- leukemia
disease_term:
preferred_term: acute lymphoblastic leukemia
term:
id: MONDO:0004967
label: acute lymphoblastic leukemia
has_subtypes:
- name: B-ALL with ETV6-RUNX1
display_name: B-ALL with ETV6-RUNX1 (t(12;21))
description: >-
Most common B-ALL subtype in children (about 25%). Cryptic t(12;21)(p13;q22)
fuses ETV6 (TEL) with RUNX1 (AML1), producing a chimeric transcription factor
that disrupts hematopoietic transcriptional programs. Generally favorable
prognosis with cure rates above 90% on contemporary regimens, although a
subset relapses late.
- name: B-ALL with TCF3-PBX1
display_name: B-ALL with TCF3-PBX1 (t(1;19))
description: >-
Approximately 5% of childhood B-ALL. The t(1;19)(q23;p13) translocation fuses
TCF3 (E2A) with PBX1, generating an oncogenic transcription factor that
activates aberrant target genes and arrests B-cell differentiation.
Historically high CNS relapse risk; outcomes are now favorable with
intensified, CNS-directed regimens.
- name: B-ALL with KMT2A rearrangement
display_name: B-ALL with KMT2A (MLL) rearrangement
description: >-
KMT2A (MLL) rearrangements with diverse partner genes (notably AFF1/AF4 in
t(4;11)) define a high-risk B-ALL subtype that predominates in infants under
one year of age. The fusion produces aberrant histone methylation patterns
and a distinctive pro-B / mixed-lineage immunophenotype, and is associated
with hyperleukocytosis and inferior outcomes.
- name: Ph+ ALL
display_name: Philadelphia chromosome-positive ALL (BCR-ABL1)
description: >-
B-ALL defined by the t(9;22)(q34;q11) translocation creating BCR-ABL1, most
often the p190 isoform. Comprises 20-30% of adult B-ALL and 3-5% of pediatric
B-ALL. The constitutively active BCR-ABL1 tyrosine kinase drives leukemic
transformation of B-lymphoid progenitors. IKZF1 deletions cooperate in most
cases. Targetable with tyrosine kinase inhibitors (imatinib, dasatinib,
ponatinib) combined with chemotherapy, blinatumomab, and allogeneic stem
cell transplantation.
evidence:
- reference: PMID:41251904
reference_title: "Philadelphia chromosome-positive acute lymphoblastic leukemia: exploring microRNA-based strategies to improve outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is characterized by the BCR::ABL1 fusion gene resulting from the translocation t(9;22)."
explanation: This abstract directly defines the Ph+ ALL subtype as B-ALL bearing the BCR-ABL1 fusion from t(9;22), matching the subtype description.
- name: Ph-like ALL
display_name: Philadelphia chromosome-like ALL (BCR-ABL1-like)
description: >-
A high-risk B-ALL subtype with a gene expression profile resembling Ph+ ALL
but lacking the BCR-ABL1 fusion. Comprises approximately 10-15% of pediatric
and more than 25% of adult B-ALL. Driven by diverse kinase- and cytokine
receptor-activating lesions including CRLF2 rearrangements (often with JAK1/JAK2
mutations), and rearrangements involving ABL1, ABL2, PDGFRB, EPOR, and IL7R.
IKZF1 alterations are a near-universal cooperating lesion. Outcomes are poor
on conventional therapy, but specific lesions are amenable to TKIs (ABL-class
fusions) or JAK inhibitors (CRLF2/JAK pathway).
evidence:
- reference: PMID:23523389
reference_title: "Acute lymphoblastic leukaemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Ten to 12 percent of B-ALL cases exhibit a gene expression profile similar to that of BCR-ABL1 ALL but are BCR-ABL1-negative, commonly show IKZF1 alteration, and have a poor outcome"
explanation: This Lancet review establishes the BCR-ABL1-like (Ph-like) subtype as a B-ALL with a Ph+-like expression signature, frequent IKZF1 alteration, and poor outcome, matching the subtype description.
- name: T-ALL
display_name: T-cell acute lymphoblastic leukemia
description: >-
Approximately 10-15% of pediatric and 25% of adult ALL, arising from
immature T-lymphoid precursors. Frequent activating NOTCH1 mutations
(about 50-60%), CDKN2A/B deletions, and aberrant expression of T-cell
transcription factors (TAL1, LMO1/2, TLX1/3, HOXA). Often presents with
mediastinal mass, hyperleukocytosis, and CNS involvement. Includes the
early T-cell precursor (ETP-ALL) subset, which has stem/myeloid features
and historically poorer outcomes.
evidence:
- reference: PMID:15472075
reference_title: "Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1."
explanation: This Science paper establishes the high frequency of NOTCH1 activating mutations in T-ALL, supporting the molecular description of this subtype.
pathophysiology:
- name: Acquisition of Initiating Genetic Lesion in Lymphoid Progenitor
description: >-
A founding cytogenetic or molecular lesion - typically a chromosomal
translocation creating a chimeric oncogene (e.g., ETV6-RUNX1, TCF3-PBX1,
KMT2A fusions, BCR-ABL1) or aneuploidy (high hyperdiploidy, hypodiploidy) -
occurs in a B- or T-lymphoid progenitor. For many B-ALL subtypes initiation
is thought to occur in utero, with covert pre-leukemic clones persisting
until later promotional events.
cell_types:
- preferred_term: lymphoid lineage restricted progenitor cell
term:
id: CL:0000838
label: lymphoid lineage restricted progenitor cell
evidence:
- reference: PMID:23523389
reference_title: "Acute lymphoblastic leukaemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genome-wide profiling of germline and leukaemic cell DNA has identified novel submicroscopic structural genetic changes and sequence mutations that contribute to leukaemogenesis, define new disease subtypes, affect responsiveness to treatment, and might provide novel prognostic markers and therapeutic targets for personalised medicine."
explanation: This Lancet review establishes that genome-wide profiling has identified recurrent genetic lesions that contribute to ALL leukemogenesis and define disease subtypes, supporting the founding-lesion model.
- reference: PMID:23523389
reference_title: "Acute lymphoblastic leukaemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the multi-step natural history of ALL from its initiation (usually in utero) through its largely covert evolution to overt disease"
explanation: This Lancet review states that ALL initiation usually occurs in utero, with covert evolution to overt disease, supporting the prenatal-origin model for many B-ALL subtypes.
downstream:
- target: Disruption of Lymphoid Transcriptional Program
description: Fusion oncoproteins and aneuploidy reprogram lymphoid transcription
- name: Disruption of Lymphoid Transcriptional Program
description: >-
Chimeric transcription factors (ETV6-RUNX1, TCF3-PBX1, KMT2A fusions) and
activating signaling lesions (BCR-ABL1, NOTCH1) corrupt the transcriptional
networks that normally direct stage-specific B- and T-cell differentiation.
KMT2A fusions deregulate H3K79 and H3K4 methylation at HOXA cluster genes;
NOTCH1 gain-of-function in T-ALL drives MYC and PI3K-AKT target genes.
biological_processes:
- preferred_term: regulation of transcription by RNA polymerase II
modifier: ABNORMAL
term:
id: GO:0006357
label: regulation of transcription by RNA polymerase II
downstream:
- target: Block in Lymphoid Differentiation
description: Aberrant transcription arrests lymphoid progenitors at an immature stage
- target: Constitutive Proliferation and Survival Signaling
description: Aberrant signaling pathways drive cell-cycle progression and apoptosis evasion
- name: Block in Lymphoid Differentiation
description: >-
Cooperating lesions, including IKZF1 (Ikaros), PAX5, and EBF1 deletions in
B-ALL and dominant-negative effects on E2A/RUNX1 targets, arrest cells at an
immature lymphoblast stage. Cells express lineage markers (CD19/CD22/CD10
for B-ALL; CD7/CD3 for T-ALL) but fail to complete normal lymphoid
maturation.
cell_types:
- preferred_term: common lymphoid progenitor
term:
id: CL:0000051
label: common lymphoid progenitor
biological_processes:
- preferred_term: lymphocyte differentiation
modifier: DECREASED
term:
id: GO:0030098
label: lymphocyte differentiation
evidence:
- reference: PMID:23523389
reference_title: "Acute lymphoblastic leukaemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Most commonly altered are transcriptional regulators of B lymphoid development (eg, PAX5, IZKF1, and EBF1) in more than two-thirds of B-ALL cases"
explanation: This Lancet review documents that more than two-thirds of B-ALL cases harbor alterations in transcriptional regulators of B-lymphoid development (PAX5, IKZF1, EBF1), supporting the differentiation-block mechanism.
downstream:
- target: Clonal Expansion of Lymphoblasts
description: Differentiation-arrested cells accumulate as a proliferating clone
- name: Constitutive Proliferation and Survival Signaling
description: >-
Driver lesions activate proliferative and anti-apoptotic signaling
independently of normal regulation. BCR-ABL1 activates RAS-MAPK, PI3K-AKT,
and JAK-STAT pathways; NOTCH1 mutations sustain MYC and PI3K-AKT signaling
in T-ALL; KMT2A fusions upregulate HOXA9/MEIS1 driving self-renewal. The
net effect is increased proliferation and resistance to apoptosis.
biological_processes:
- preferred_term: signal transduction
modifier: INCREASED
term:
id: GO:0007165
label: signal transduction
- preferred_term: apoptotic process
modifier: DECREASED
term:
id: GO:0006915
label: apoptotic process
evidence:
- reference: PMID:15472075
reference_title: "Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1."
explanation: This landmark paper establishes that activating NOTCH1 mutations are present in more than half of T-ALL cases, supporting the role of NOTCH-driven proliferative signaling in T-ALL.
downstream:
- target: Clonal Expansion of Lymphoblasts
description: Proliferative drive combined with apoptosis resistance fuels expansion
- name: Clonal Expansion of Lymphoblasts
description: >-
Differentiation-blocked, proliferation-driven lymphoblasts undergo clonal
expansion in the bone marrow and disseminate into peripheral blood and
extramedullary sites (lymph nodes, spleen, liver, CNS, mediastinum, gonads).
cell_types:
- preferred_term: common lymphoid progenitor
term:
id: CL:0000051
label: common lymphoid progenitor
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
downstream:
- target: Bone Marrow Failure
description: Marrow infiltration displaces normal hematopoiesis
- target: Extramedullary Disease
description: Blasts infiltrate lymphoid organs, CNS, mediastinum, and other sites
- name: Bone Marrow Failure
description: >-
Replacement of normal marrow by lymphoblasts suppresses production of red
cells, platelets, and functional neutrophils, producing the cytopenias that
underlie most clinical manifestations of ALL (anemia-related fatigue,
bleeding from thrombocytopenia, and infection from neutropenia).
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
biological_processes:
- preferred_term: hematopoiesis
modifier: DECREASED
term:
id: GO:0030097
label: hemopoiesis
evidence:
- reference: PMID:23523389
reference_title: "Acute lymphoblastic leukaemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Four to 6 weeks of remission-induction treatment eradicates the initial leukaemic cell burden and restores normal haematopoiesis"
explanation: This Lancet review states that effective induction therapy must eradicate the leukaemic burden in the marrow and restore normal haematopoiesis, indicating that lymphoblast accumulation in marrow has displaced normal hematopoiesis prior to treatment (i.e., bone marrow failure).
- name: Extramedullary Disease
description: >-
Lymphoblasts infiltrate extramedullary sites, producing lymphadenopathy,
hepatosplenomegaly, mediastinal mass (especially in T-ALL), and CNS or
testicular involvement that can act as sanctuary sites for relapse if not
addressed by prophylaxis.
cell_types:
- preferred_term: common lymphoid progenitor
term:
id: CL:0000051
label: common lymphoid progenitor
phenotypes:
- category: Hematologic
name: Pancytopenia
frequency: VERY_FREQUENT
description: >-
Reduction in red cells, platelets, and functional neutrophils as marrow is
replaced by lymphoblasts, underlying anemia, bleeding, and infection risk.
phenotype_term:
preferred_term: Pancytopenia
term:
id: HP:0001876
label: Pancytopenia
- category: Hematologic
name: Anemia
frequency: VERY_FREQUENT
description: >-
Reduced red blood cell production from marrow infiltration produces fatigue
and pallor.
phenotype_term:
preferred_term: Anemia
term:
id: HP:0001903
label: Anemia
- category: Hematologic
name: Thrombocytopenia
frequency: VERY_FREQUENT
description: >-
Reduced platelet production causes bruising, petechiae, and bleeding.
phenotype_term:
preferred_term: Thrombocytopenia
term:
id: HP:0001873
label: Thrombocytopenia
- category: Hematologic
name: Leukocytosis with Circulating Blasts
frequency: FREQUENT
description: >-
Many patients present with elevated total leukocyte counts driven by
circulating lymphoblasts; KMT2A-rearranged and Ph+ ALL particularly tend to
present with hyperleukocytosis.
phenotype_term:
preferred_term: Leukocytosis
term:
id: HP:0001974
label: Increased total leukocyte count
- category: Constitutional
name: Fatigue
frequency: VERY_FREQUENT
description: >-
Fatigue from anemia and the systemic effects of leukemia.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Constitutional
name: Fever
frequency: FREQUENT
description: >-
Fever may be due to leukemic disease itself or to infection in the setting
of neutropenia.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
- category: Lymphatic
name: Lymphadenopathy
frequency: FREQUENT
description: >-
Enlarged lymph nodes from leukemic infiltration, common in both B-ALL and
T-ALL.
phenotype_term:
preferred_term: Lymphadenopathy
term:
id: HP:0002716
label: Lymphadenopathy
- category: Abdominal
name: Hepatosplenomegaly
frequency: FREQUENT
description: >-
Hepatomegaly and splenomegaly from leukemic infiltration and extramedullary
hematopoiesis.
phenotype_term:
preferred_term: Hepatosplenomegaly
term:
id: HP:0001433
label: Hepatosplenomegaly
- category: Skeletal
name: Bone Pain
frequency: FREQUENT
description: >-
Bone pain, particularly in long bones, from marrow expansion by leukemic
infiltrate; common presenting complaint in pediatric ALL.
phenotype_term:
preferred_term: Bone pain
term:
id: HP:0002653
label: Bone pain
- category: Hemorrhagic
name: Bleeding Tendency
frequency: FREQUENT
description: >-
Bruising, petechiae, mucosal bleeding from thrombocytopenia.
phenotype_term:
preferred_term: Increased bleeding tendency
term:
id: HP:0001892
label: Abnormal bleeding
- category: Infectious
name: Recurrent Infections
frequency: FREQUENT
description: >-
Increased susceptibility to bacterial, viral, and fungal infections from
neutropenia and impaired humoral immunity.
phenotype_term:
preferred_term: Recurrent infections
term:
id: HP:0002719
label: Recurrent infections
- category: Neurological
name: CNS Involvement
frequency: OCCASIONAL
description: >-
Leukemic infiltration of the leptomeninges may produce headache, cranial
nerve palsies, or altered mental status; CNS is a sanctuary site requiring
intrathecal prophylaxis.
phenotype_term:
preferred_term: CNS leukemic infiltration
term:
id: HP:0100006
label: Neoplasm of the central nervous system
- category: Respiratory
name: Mediastinal Mass
frequency: FREQUENT
subtype: T-ALL
description: >-
Anterior mediastinal mass with possible tracheal compression and
superior vena cava syndrome is characteristic of T-ALL.
phenotype_term:
preferred_term: Anterior mediastinal mass
term:
id: HP:0033827
label: Anterior mediastinal mass
biochemical:
- name: Peripheral Blood and Bone Marrow Blasts
notes: >-
Diagnosis requires demonstration of lymphoblasts comprising at least 20%
of bone marrow nucleated cells (or characteristic immunophenotype/genetics
in extramedullary disease).
- name: Immunophenotyping
notes: >-
Flow cytometry distinguishes B-ALL (CD19+, CD22+, CD79a+, often CD10+,
TdT+, surface Ig variable) from T-ALL (cytoplasmic CD3+, CD7+, variable
CD2/CD4/CD5/CD8). Aberrant myeloid antigen expression occurs in some Ph+
and KMT2A-rearranged cases. Early T-cell precursor ALL (ETP-ALL) shows
CD8-, CD1a-, weak CD5, with stem/myeloid markers.
- name: Cytogenetics and Molecular Diagnostics
notes: >-
Karyotyping, FISH, and RT-PCR or RNA sequencing detect defining
abnormalities including ETV6-RUNX1, TCF3-PBX1, KMT2A rearrangements,
BCR-ABL1, hyperdiploidy, hypodiploidy, and Ph-like (BCR-ABL1-like)
signatures. Used for risk stratification and selection of targeted therapy.
- name: Minimal Residual Disease (MRD)
notes: >-
Quantitative PCR for fusion transcripts (BCR-ABL1, MLL fusions) or
multiparameter flow cytometry tracks residual disease at end of induction
and consolidation; MRD positivity is the strongest single predictor of
relapse and informs intensification or transplant decisions.
genetic:
- name: BCR-ABL1 Fusion (Philadelphia chromosome)
association: Defining lesion of Ph+ ALL subtype
gene_term:
preferred_term: ABL1
term:
id: hgnc:76
label: ABL1
notes: >-
The t(9;22)(q34;q11) translocation creates a BCR (hgnc:1014) - ABL1
(hgnc:76) fusion, typically as the p190 isoform in ALL (versus p210 in CML).
Defines Ph+ ALL and is the major driver in this subtype; targetable with
tyrosine kinase inhibitors.
- name: ETV6-RUNX1 Fusion
association: Defining lesion of ETV6-RUNX1 B-ALL subtype
gene_term:
preferred_term: RUNX1
term:
id: hgnc:10471
label: RUNX1
notes: >-
The cryptic t(12;21)(p13;q22) fuses ETV6 (TEL; hgnc:3495) with RUNX1
(AML1; hgnc:10471). Most common recurrent translocation in childhood
B-ALL; favorable prognosis.
- name: TCF3-PBX1 Fusion
association: Defining lesion of TCF3-PBX1 B-ALL subtype
gene_term:
preferred_term: PBX1
term:
id: hgnc:8632
label: PBX1
notes: >-
The t(1;19)(q23;p13) fuses TCF3 (E2A; hgnc:11633) with PBX1 (hgnc:8632),
producing an oncogenic chimeric transcription factor; historically high
CNS relapse risk.
- name: KMT2A Rearrangement
association: Defining lesion of KMT2A-rearranged B-ALL subtype
gene_term:
preferred_term: KMT2A
term:
id: hgnc:7132
label: KMT2A
notes: >-
KMT2A (MLL) rearrangements with diverse partners (most commonly AFF1/AF4
in t(4;11)) deregulate HOXA-cluster transcription; predominate in infant
B-ALL with poor prognosis.
- name: NOTCH1 Activating Mutations
association: Frequent driver in T-ALL
gene_term:
preferred_term: NOTCH1
term:
id: hgnc:7881
label: NOTCH1
notes: >-
Activating NOTCH1 mutations occur in approximately 50-60% of T-ALL cases,
sustaining MYC and PI3K-AKT signaling and lymphoblast self-renewal.
- name: IKZF1 Deletion
association: Cooperating mutation, especially in Ph+/Ph-like ALL
gene_term:
preferred_term: IKZF1
term:
id: hgnc:13176
label: IKZF1
notes: >-
IKZF1 (Ikaros) deletions occur in 70-80% of Ph+ ALL and in Ph-like ALL,
impair B-cell development, and confer adverse prognosis.
evidence:
- reference: PMID:19129520
reference_title: "Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell-progenitor ALL."
explanation: This NEJM study established that IKZF1 deletion is an independent predictor of poor outcome in B-cell ALL, supporting its role as an adverse cooperating lesion.
- name: CDKN2A/CDKN2B Deletion
association: Frequent cooperating lesion in T-ALL and B-ALL
gene_term:
preferred_term: CDKN2A
term:
id: hgnc:1787
label: CDKN2A
notes: >-
Biallelic deletion of CDKN2A/CDKN2B at 9p21 is one of the most common
secondary lesions in ALL and removes p16/INK4A and p14/ARF tumor
suppressor function. CDKN2B (hgnc:1788) is co-deleted at the same 9p21
locus.
treatments:
- name: Induction Chemotherapy
description: >-
Multi-agent induction (commonly vincristine, anthracycline, corticosteroid,
and L-asparaginase, with intrathecal therapy) achieves morphologic complete
remission in greater than 90% of children and most adults.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
therapeutic_agent:
- preferred_term: vincristine
term:
id: CHEBI:28445
label: vincristine
- name: Consolidation and Maintenance Chemotherapy
description: >-
Consolidation intensification followed by 2-3 years of low-intensity
maintenance (mercaptopurine, methotrexate) is required to eradicate
residual disease and prevent relapse, particularly in B-ALL.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: CNS-Directed Therapy
description: >-
Intrathecal chemotherapy (methotrexate, cytarabine, hydrocortisone) with or
without cranial irradiation prevents and treats CNS leukemia; CNS-directed
therapy is mandatory because the CNS is a sanctuary site.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
- name: Tyrosine Kinase Inhibitors
description: >-
Addition of TKIs (imatinib, dasatinib, ponatinib) to chemotherapy
transforms outcomes in Ph+ ALL; dasatinib provides better CNS penetration,
and ponatinib targets T315I-mutated disease. TKIs are continued through
induction, consolidation, and maintenance. ABL-class TKIs and JAK inhibitors
are also being explored in Ph-like ALL with kinase-activating fusions.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: imatinib
term:
id: CHEBI:45783
label: imatinib
- preferred_term: dasatinib
term:
id: CHEBI:49375
label: dasatinib (anhydrous)
- preferred_term: ponatinib
term:
id: CHEBI:78543
label: ponatinib
- name: Blinatumomab (CD19-CD3 BiTE)
description: >-
CD19-directed CD3-engaging bispecific antibody effective for relapsed/
refractory B-ALL and for MRD-positive disease; increasingly incorporated
into frontline regimens, including in Ph+ ALL combinations.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: blinatumomab
term:
id: NCIT:C62528
label: Blinatumomab
- name: Inotuzumab Ozogamicin
description: >-
Anti-CD22 antibody-drug conjugate for relapsed/refractory CD22+ B-ALL;
delivers calicheamicin payload after CD22 binding.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: inotuzumab ozogamicin
term:
id: NCIT:C71542
label: Inotuzumab Ozogamicin
- name: CD19 CAR-T Cell Therapy
description: >-
CD19-directed chimeric antigen receptor T-cell therapy (e.g., tisagenlecleucel,
brexucabtagene autoleucel) achieves durable remissions in relapsed/refractory
pediatric and adult B-ALL.
treatment_term:
preferred_term: immunotherapy
term:
id: MAXO:0001002
label: immunotherapy procedure
- name: Allogeneic Hematopoietic Stem Cell Transplantation
description: >-
Allogeneic transplant in first or subsequent remission for high-risk
disease (Ph+ ALL with persistent MRD, hypodiploid, KMT2A-rearranged
infant ALL, refractory T-ALL) provides graft-versus-leukemia effect.
treatment_term:
preferred_term: hematopoietic stem cell transplantation
term:
id: MAXO:0000747
label: hematopoietic stem cell transplantation
- name: Supportive Care
description: >-
Transfusion support, infection prophylaxis and treatment, tumor lysis
syndrome prevention, and management of treatment-related toxicities are
integral to ALL therapy.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
classifications:
icdo_morphology:
classification_value: Leukemia
harrisons_chapter:
- classification_value: cancer
- classification_value: hematologic malignancy
Acute lymphoblastic leukemia/lymphoma (ALL) is an aggressive neoplasm of precursor B‑ or precursor T‑lymphoid cells (B‑ALL and T‑ALL) that typically arises in the bone marrow but can involve extramedullary sites. (duffield2023internationalconsensusclassification pages 1-3, kansal2023diagnosisandmolecular pages 1-2)
Modern classification is genetics-forward. WHO 2022 (WHO‑HAEM5) and the International Consensus Classification (ICC) incorporate molecular/cytogenetic entities and transcriptome-defined subgroups to refine diagnosis and risk stratification. (kansal2023diagnosisandmolecular pages 5-7, duffield2023internationalconsensusclassification pages 1-3, yoon2024diagnosticandtherapeutic pages 1-2)
The report primarily synthesizes aggregated disease-level resources (2024 ELN recommendations; 2024 NCCN guideline excerpt; 2023 ICC classification paper; 2024 population studies and clinical trials) plus selected human cohort/clinical trial primary studies (SEER analyses; prospective phase 2; JCO trial update). (gokbuget2024managementofall pages 1-2, shah2024acutelymphoblasticleukemia pages 1-2, duffield2023internationalconsensusclassification pages 1-3, liu2024epidemiologicalcharacteristicsand pages 1-3, lu2024reduceddosechemotherapyand pages 1-2, kantarjian2024resultsofthe pages 1-3)
ALL is initiated and driven by acquired genetic lesions in lymphoid precursors (e.g., chromosomal rearrangements creating oncogenic fusions; aneuploidy; activating kinase lesions), with additional cooperating mutations and epigenetic remodeling. WHO‑HAEM5/ICC increasingly define ALL entities by such genomic features, including transcriptome-defined classes for previously “B‑other” cases. (kansal2023diagnosisandmolecular pages 5-7, duffield2023internationalconsensusclassification pages 1-3)
A 2023 pediatric-focused review summarizes that germline susceptibility includes common loci (e.g., ARID5B, CEBPE, BMI1, CDKN2A/2B) and rare inherited mutations in hematopoietic genes (ETV6, PAX5, IKZF1). It reports ~4.4% of children/adolescents with ALL carry pathogenic germline mutations in known cancer genes, and that Down syndrome confers ~20‑fold increased risk. (ekpa2023areviewof pages 2-3)
Visual evidence (RR vs UVR): Figure showing the RR relationship used in this analysis is provided in (little2024solarultravioletradiation media 5ae23b8e).
No specific protective genetic variants or protective exposures were directly extractable from the retrieved evidence set. The UVR literature is mixed (some prior work suggests protection with higher solar exposure, but the 2024 US SEER ecological study reported the opposite direction for ALL). (little2024solarultravioletradiation pages 8-9)
Direct GxE analyses were not present in the retrieved corpus. However, a 2023 pediatric review highlights maternal exposures (tobacco smoke, air pollution, BMI) being associated with neonatal DNA methylation changes, suggesting a plausible epigenetic mediation pathway for environmental effects on leukemia risk. (ekpa2023areviewof pages 2-3)
A 223-case pediatric clinicopathological series provides concrete presentation frequencies: - Pallor/anemia: 93.3% (208/223) - Fever: 89.7% (200/223) - Hepatomegaly: 89.2% (199/223) - Splenomegaly: 74.9% (167/223) - Lymphadenopathy: 63.7% (142/223) - Bony tenderness/bone pain: 50.7% (113/223) - Bleeding manifestations: 35.9% - Joint involvement/arthritis-like: 25.6% - CNS involvement at diagnosis: ~1.3% - Testicular enlargement: ~0.44% (karim2023diagnosticclueof pages 2-4)
A 2024 musculoskeletal-mimic report/review context also emphasizes that 15–30% of ALL cases may present with isolated, persistent osteo‑articular complaints that can delay diagnosis and can be masked by corticosteroids. (talukder2024acutelymphoblasticleukemia pages 1-3, karim2023diagnosticclueof pages 5-6)
From the same 223-case series: - Leukocytosis: 49.4% (including WBC >50,000/µL in 24.2%; WBC >100,000/µL in 15.2%) - Leukopenia: 18.8% - Pancytopenia at diagnosis: 18.8% - Decreased age-adjusted neutrophil percentage: 93.7% (karim2023diagnosticclueof pages 2-4, karim2023diagnosticclueof pages 1-2)
(Provide as starting points; exact mapping may be adjusted during ontology curation.) - Fever HP:0001945 - Pallor HP:0000980 - Anemia HP:0001903 - Thrombocytopenia HP:0001873; Bleeding tendency HP:0001892 - Neutropenia HP:0001875; Leukocytosis HP:0001974; Leukopenia HP:0001882; Pancytopenia HP:0001876 - Hepatomegaly HP:0002240; Splenomegaly HP:0001744 - Lymphadenopathy HP:0002716 - Bone pain HP:0002653; Bone tenderness HP:0030830 - Arthritis/Joint pain HP:0001369 - CNS involvement can manifest as headache HP:0002315, cranial nerve palsy HP:0001291 (clinical term selection depends on documentation). (karim2023diagnosticclueof pages 2-4)
While the retrieved evidence set did not include formal QoL instrument outcomes, the phenotype spectrum above implies substantial functional impact via fatigue, pain, infection risk, and bleeding risk, and treatment is associated with significant toxicity; ELN 2024 explicitly includes supportive care and late effects in its scope. (gokbuget2024managementofall pages 1-2)
WHO‑HAEM5/ICC classify many ALL entities by recurrent genetic lesions. Examples explicitly discussed in the retrieved evidence include: - BCR::ABL1 (Philadelphia chromosome) / Ph+ ALL and BCR::ABL1‑like (“Ph‑like”) (yoon2024diagnosticandtherapeutic pages 1-2, kansal2023diagnosisandmolecular pages 5-7) - ETV6::RUNX1, TCF3::PBX1, KMT2A (MLL) rearrangements, aneuploidy classes (high hyperdiploidy, hypodiploidy), and newer entities derived from genomic/transcriptome profiling previously within “B‑other”. (kansal2023diagnosisandmolecular pages 5-7, kansal2023diagnosisandmolecular pages 4-5)
The ICC 2022 framework further subdivides BCR::ABL1+ cases (lymphoid-only vs multilineage) and introduces multiple new genetic categories and provisional gene-expression-defined entities. (duffield2023internationalconsensusclassification pages 1-3)
The 2023 pediatric review highlights epigenome-wide associations of maternal exposures (e.g., smoking) with neonatal methylation changes (e.g., AHRR CpG cg05575921), consistent with epigenetic mediation hypotheses for leukemia risk. (ekpa2023areviewof pages 2-3)
Direct pathogen causation is not established for ALL in general; infection-related hypotheses (population mixing/delayed infection) are discussed as etiologic theories in pediatric literature. (ekpa2023areviewof pages 2-3, little2024solarultravioletradiation pages 11-11)
1) Initiating lesions (chromosomal rearrangements/aneuploidy/kinase activation) occur in developing lymphoid precursors. (kansal2023diagnosisandmolecular pages 5-7, duffield2023internationalconsensusclassification pages 1-3) 2) Differentiation arrest and uncontrolled proliferation yield expanding lymphoblast clones in marrow and/or extramedullary sites. A 2024 adult review describes ALL as “marked by abnormal clones with arrested differentiation and uncontrolled proliferation in bone marrow and extramedullary sites.” (yoon2024diagnosticandtherapeutic pages 1-2) 3) Marrow failure causes cytopenias (anemia → pallor/fatigue; thrombocytopenia → bleeding; neutropenia → infection/fever) and may coexist with leukocytosis and circulating blasts. (karim2023diagnosticclueof pages 2-4) 4) Tissue infiltration produces hepatosplenomegaly, lymphadenopathy, bone pain/periosteal involvement, and less commonly CNS/testicular disease. (karim2023diagnosticclueof pages 2-4)
The retrieved WHO‑HAEM5/ICC sources emphasize that subtypes are increasingly organized around: - Kinase signaling activation (e.g., BCR::ABL1 and Ph‑like lesions), affecting therapy selection (TKIs; immunotherapy-based regimens) and risk. (yoon2024diagnosticandtherapeutic pages 1-2, kantarjian2024ponatinib‐reviewofhistorical pages 10-11) - Transcription factor and developmental programs identified by gene-expression clustering (ICC) that refine biologic taxonomy beyond classical cytogenetics. (duffield2023internationalconsensusclassification pages 1-3)
Primary site is the bone marrow with systemic hematopoietic involvement; common secondary involvement includes liver, spleen, lymph nodes, and bone (pain/tenderness). Less commonly at diagnosis: CNS and testis. (karim2023diagnosticclueof pages 2-4)
ALL has a strong pediatric incidence peak but occurs across the lifespan. Median age at diagnosis in the US is 17 years, with 53.5% diagnosed before age 20. (shah2024acutelymphoblasticleukemia pages 1-2)
Clinically acute presentation is typical; untreated disease progresses rapidly with complications from cytopenias and infiltration. Response and relapse risk are strongly influenced by molecular subtype and depth of remission measured by MRD. (gokbuget2024managementofall pages 6-6)
Most ALL is sporadic (somatic). A minority reflects germline predisposition syndromes/variants (e.g., Down syndrome and inherited variants in ETV6/PAX5/IKZF1). (ekpa2023areviewof pages 2-3)
MRD is central to prognosis and therapeutic decision-making in adult ALL. - Threshold commonly used: 0.01% (10−4), aligned to typical assay sensitivity; ELN notes each log increase in MRD shortens time to hematologic relapse. (gokbuget2024managementofall pages 6-6) - Method performance: - Expert review: RQ‑PCR sensitivity ~10−5; multiparametric flow cytometry ~10−4; PCR/HTS may reach ~10−6 depending on input. (sebastian2024howitreat pages 1-2, yoon2024diagnosticandtherapeutic pages 6-8) - Timing: ELN emphasizes early vs later MRD timepoints (often ~2–3 months) to guide escalation/de‑escalation. (gokbuget2024managementofall pages 6-6)
NCCN excerpt includes traditional high-risk features in one trial framework: age ≥35 years, time to CR >4 weeks, or high WBC (>30×10^9/L for B-lineage; >100×10^9/L for T-lineage). (shah2024acutelymphoblasticleukemia pages 3-5)
The 2024 European LeukemiaNet (ELN) recommendations emphasize risk-adapted adult ALL management driven by baseline prognostic factors and MRD to determine intensity, incorporation of immunotherapies, and transplant indications. (gokbuget2024managementofall pages 1-2)
| Modality/agent | Target or mechanism | Key use-case | Selected 2024 efficacy/statistics | Key toxicities / implementation notes | Key 2024 sources with URL and pub month/year |
|---|---|---|---|---|---|
| Pediatric-inspired multi-agent chemotherapy (adult AYA/fit adults); e.g., pediatric-inspired regimens, Hyper-CVAD variants | Multi-agent cytotoxic therapy targeting proliferating lymphoblasts; often includes asparaginase, vincristine, steroids, anthracycline, methotrexate/6-MP phases | Standard frontline backbone for Ph-negative ALL in younger/fit adults; adapted intensity by age/fitness | ELN 2024: pediatric-based regimens are standard up to ~45–55 years and adult Ph-negative ALL CR rates are ~90% in many groups; expert review notes ~20% 5-year OS benefit in AYA with pediatric-inspired regimens vs traditional adult regimens (gokbuget2024managementofall pages 1-2, sebastian2024howitreat pages 1-2) | Age/fitness constrained; asparaginase toxicity, infections, hepatic/pancreatic toxicity, thrombosis; obesity adversely affects OS in adults and may shape supportive-care intensity (sebastian2024howitreat pages 1-2, johnston2024socioeconomicdeterminantsof pages 1-2) | Gökbuget et al., Blood (May 2024) https://doi.org/10.1182/blood.2023023568 (gokbuget2024managementofall pages 1-2); Sebastian, Clin Hematol Int (May 2024) https://doi.org/10.46989/001c.117026 (sebastian2024howitreat pages 1-2); Johnston et al., Blood Adv (Dec 2024) https://doi.org/10.1182/bloodadvances.2023011862 (johnston2024socioeconomicdeterminantsof pages 1-2) |
| TKIs for Ph+ ALL (imatinib, dasatinib, ponatinib) | Inhibit BCR::ABL1 kinase signaling; ponatinib active against T315I and other resistant mutants | Frontline Ph+ ALL; often with reduced-intensity chemo or with blinatumomab; salvage/bridge contexts also used | Ponatinib review: PONALFIL post-induction CMR 47% rising to 71% in consolidation; 3-year OS 97%, EFS 70%; PhALLCON MRD-negative CR 34.4% with ponatinib vs 16.7% imatinib, and in age ≥60 years 40.0% vs 10.3%, median PFS 22.5 vs 8.3 months (kantarjian2024ponatinib‐reviewofhistorical pages 10-11) | Cardiovascular/arterial occlusive risk with ponatinib; pancreatitis reported; TKI selection depends on mutation profile, age, comorbidities, CNS strategy, transplant plan (kantarjian2024ponatinib‐reviewofhistorical pages 10-11, sebastian2024howitreat pages 5-7) | Kantarjian et al., Am J Hematol (May 2024) https://doi.org/10.1002/ajh.27355 (kantarjian2024ponatinib‐reviewofhistorical pages 10-11); Sebastian, Clin Hematol Int (May 2024) https://doi.org/10.46989/001c.117026 (sebastian2024howitreat pages 5-7) |
| Blinatumomab | CD19xCD3 bispecific T-cell engager; redirects T cells to lyse CD19+ B-ALL cells | MRD-positive B-ALL; R/R B-ALL; increasingly frontline consolidation/low-intensity induction component in Ph-negative and Ph+ disease | Frontline Ph-negative phase 2 (reduced-dose chemo → blinatumomab): CRc 94% after 2 weeks blina, MRD-negative 86%; with up to 4 weeks, CR 100% and MRD-negative 89%; 1-year OS 97.1%, PFS 82.2% (NCT05557110) (lu2024reduceddosechemotherapyand pages 1-2). Review/guideline: MRD response ~80% and hematologic relapse-free survival 61% in MRD-directed setting; survival benefit also emerging in MRD-negative frontline consolidation (stelljes2024ph−allimmunotherapy pages 1-2) | Continuous IV infusion standard; CRS and neurotoxicity/ICANS require monitoring; in Lu 2024 ICANS 14% (all grade 1), grade ≥3 CRS 9% (lu2024reduceddosechemotherapyand pages 1-2) | Lu et al., J Hematol Oncol (Sep 2024) https://doi.org/10.1186/s13045-024-01597-8 (lu2024reduceddosechemotherapyand pages 1-2); Stelljes, Hematology (Dec 2024) https://doi.org/10.1182/hematology.2024000531 (stelljes2024ph−allimmunotherapy pages 1-2); Gökbuget et al., Blood (May 2024) https://doi.org/10.1182/blood.2023023568 (gokbuget2024managementofall pages 1-2) |
| Inotuzumab ozogamicin | Anti-CD22 antibody-drug conjugate delivering calicheamicin | Approved for R/R CD22+ B-ALL; increasingly used in frontline low-intensity regimens in older/unfit adults; MRD eradication / bridge to HSCT / sequencing with CAR-T | 2024 reviews summarize strong efficacy in R/R disease and promising frontline combinations with low-intensity chemotherapy or blinatumomab; used to eliminate MRD and bridge to HSCT/CAR-T, but article excerpt does not provide one uniform 2024 pooled ORR/OS estimate across settings (kantarjian2024inotuzumabozogamicinin pages 15-17, gokbuget2024managementofall pages 21-22) | Key risk is veno-occlusive disease/sinusoidal obstruction syndrome, especially pre-HSCT; fractionated dosing and transplant timing matter (kantarjian2024inotuzumabozogamicinin pages 15-17) | Kantarjian et al., Cancer (Aug 2024) https://doi.org/10.1002/cncr.35505 (kantarjian2024inotuzumabozogamicinin pages 15-17); Gökbuget et al., Blood (May 2024) https://doi.org/10.1182/blood.2023023568 (gokbuget2024managementofall pages 21-22) |
| Chemo-free / near chemo-free TKI + blinatumomab for Ph+ ALL (e.g., ponatinib + blinatumomab; dasatinib + blinatumomab) | Dual targeting of BCR::ABL1 signaling plus CD19-directed T-cell cytotoxicity | Frontline Ph+ ALL; increasingly used to reduce/avoid conventional chemotherapy and sometimes HSCT | Ponatinib + blinatumomab (JCO 2024): CMR 83% overall (67% after course 1), NGS-MRD negativity 98%, only 2/60 underwent HSCT, 3-year OS 91%, EFS 77%, median follow-up 24 months (kantarjian2024resultsofthe pages 1-3, kantarjian2024resultsofthe pages 3-4). D-ALBA long-term: 4-year/approximately 53-month DFS 75.8%, OS 80.7%, early molecular responders had no events (kantarjian2024ponatinib‐reviewofhistorical pages 10-11) | CNS relapse remains an issue in chemo-free Ph+ regimens; ponatinib vascular toxicities; blinatumomab CRS/neurotoxicity; transplant role becoming more selective (kantarjian2024resultsofthe pages 3-4, kantarjian2024ponatinib‐reviewofhistorical pages 10-11) | Kantarjian et al., J Clin Oncol (Dec 2024) https://doi.org/10.1200/jco.24.00272 (kantarjian2024resultsofthe pages 1-3); Foà et al., J Clin Oncol (Mar 2024) https://doi.org/10.1200/jco.23.01075 (kantarjian2024ponatinib‐reviewofhistorical pages 10-11) |
| CAR-T cell therapy (CD19-directed; pediatric and adult B-ALL) | Autologous engineered T cells targeting CD19 on B lymphoblasts | Standard for selected R/R B-ALL; bridge or alternative to HSCT; pediatric/young adult use especially established | 2024 treatment reviews state CAR-T is standard in R/R BCP-ALL and has demonstrated major efficacy, but the provided contexts here do not include a single 2024 trial with reportable ORR/OS figures for inclusion (stelljes2024ph−allimmunotherapy pages 1-2, kantarjian2024inotuzumabozogamicinin pages 15-17) | CRS, ICANS, prolonged cytopenias, hypogammaglobulinemia; manufacturing/access/logistics and disease burden at infusion are major real-world constraints; often sequenced with blinatumomab/inotuzumab/HSCT (kantarjian2024inotuzumabozogamicinin pages 15-17, stelljes2024ph−allimmunotherapy pages 1-2) | Stelljes, Hematology (Dec 2024) https://doi.org/10.1182/hematology.2024000531 (stelljes2024ph−allimmunotherapy pages 1-2); Kantarjian et al., Cancer (Aug 2024) https://doi.org/10.1002/cncr.35505 (kantarjian2024inotuzumabozogamicinin pages 15-17) |
| Allogeneic hematopoietic cell transplantation (allo-HCT) | Graft-versus-leukemia effect after myeloablative or reduced-intensity conditioning | Consolidation for high-risk disease, persistent/recurrent MRD, poor-risk genomics, or selected R/R patients in remission | ELN/expert reviews: MRD is central to transplant selection; poor MRD response supports SCT, whereas deeper MRD responses with TKI/blinatumomab regimens are reducing HSCT use in some Ph+ patients. In ponatinib+blinatumomab 2024 study, only 2 patients underwent HSCT despite 3-year OS 91% (gokbuget2024managementofall pages 6-6, kantarjian2024resultsofthe pages 3-4, gokbuget2024managementofall pages 1-2) | Transplant-related mortality, GVHD, infection, conditioning toxicity; pre-HSCT MRD level strongly predicts relapse; post-inotuzumab VOD/SOS risk requires mitigation (gokbuget2024managementofall pages 6-6, kantarjian2024inotuzumabozogamicinin pages 15-17) | Gökbuget et al., Blood (May 2024) https://doi.org/10.1182/blood.2023023568 (gokbuget2024managementofall pages 6-6); Kantarjian et al., J Clin Oncol (Dec 2024) https://doi.org/10.1200/jco.24.00272 (kantarjian2024resultsofthe pages 3-4) |
| MRD-directed therapy / response-adapted management | Uses highly sensitive residual leukemia detection (MFC, PCR, NGS) to escalate/de-escalate therapy and determine HSCT need | Cross-cutting strategy in frontline, MRD+, pre-/post-HSCT, and salvage settings | ELN 2024: threshold commonly 0.01% (10^-4); each log MRD increase worsens relapse risk; persistent/recurrent MRD should trigger therapy change; blinatumomab is the pivotal MRD-clearing agent. Review: MFC sensitivity ~10^-5; PCR/HTS up to 10^-6; key timepoints often 6–8 and 10–12 weeks (gokbuget2024managementofall pages 6-6, yoon2024diagnosticandtherapeutic pages 6-8) | Requires experienced reference labs; assay choice affects classification; marrow regeneration can confound flow; MRD does not capture extramedullary disease; low-level MRD may be intermediate-risk and still actionable (gokbuget2024managementofall pages 6-6, yoon2024diagnosticandtherapeutic pages 6-8) | Gökbuget et al., Blood (May 2024) https://doi.org/10.1182/blood.2023023568 (gokbuget2024managementofall pages 6-6); Yoon & Lee, Korean J Intern Med (Jan 2024) https://doi.org/10.3904/kjim.2023.407 (yoon2024diagnosticandtherapeutic pages 6-8) |
Table: This table summarizes major modern treatment modalities for acute lymphoblastic leukemia, including frontline, MRD-directed, relapsed/refractory, and transplant strategies. It highlights 2024 efficacy data, implementation considerations, and key sources for rapid evidence-based comparison.
A 2024 JCO trial update reports deep molecular responses with minimal HSCT use: - CMR by RT‑PCR 83% overall; MRD negativity by clono‑sequencing 98% overall; 3‑year OS 91% and EFS 77%; only 2 patients underwent HSCT; median follow-up 24 months. (kantarjian2024resultsofthe pages 1-3, kantarjian2024resultsofthe pages 3-4)
Direct abstract quote: “At a median follow-up of 24 months, the complete molecular response rate … was 83% … and the rate of measurable residual disease negativity … was 98% … The estimated 3-year overall survival rate was 91% and event-free survival rate was 77%.” (kantarjian2024resultsofthe pages 3-4)
Prospective multicenter phase 2 (NCT05557110) results: - After 2 weeks of blinatumomab: CRc 94%, MRD-negative 86%. - With up to 4 weeks: CR 100%, MRD-negative 89%. - 1‑year OS 97.1%, 1‑year PFS 82.2%; follow-up 11.5 months. (lu2024reduceddosechemotherapyand pages 1-2)
Direct abstract quote: “From September 2022 to December 2023, we conducted … (NCT05557110) … 33 (94%) achieved CRc … 30 (86%) achieving measurable residual disease (MRD) negativity … estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%.” (lu2024reduceddosechemotherapyand pages 1-2)
ELN 2024 notes persistent/recurrent MRD should prompt therapy change; blinatumomab is highlighted as the pivotal agent tested in a major MRD trial, often converting to molecular remission; many groups use MRD to decide on allo‑HCT. (gokbuget2024managementofall pages 6-6)
A 2024 pharmacogenetics review lists key genotype-toxicity associations: - For 6‑mercaptopurine (6‑MP): TPMT (e.g., TPMT2 238G>C; TPMT3B 460G>A; TPMT*3C 719A>G), NUDT15 c.415C>T, and ITPA (94C>A; IVS2+21A>C). (graiqevciuka2024implementationofpharmacogenetics pages 5-7, graiqevciuka2024implementationofpharmacogenetics pages 1-3) - For methotrexate (MTX): MTHFR C677T and A1298C variants are discussed, though the review notes evidence for some MTX markers is inconsistent and highlights SLCO1B1 as a more reliable MTX handling gene in cited literature. (graiqevciuka2024implementationofpharmacogenetics pages 5-7)
Because most ALL risk is not attributable to modifiable exposures, there is no established population-level primary prevention strategy. Nevertheless, risk literature motivates research into prenatal/early-life exposures and broader public health reduction of known hazards (e.g., ionizing radiation). (little2024solarultravioletradiation pages 1-2, ekpa2023areviewof pages 2-3)
No general population screening is established. High-risk groups (e.g., strong germline predisposition syndromes) may benefit from specialist surveillance in genetic counseling frameworks; specifics require syndrome-level guidelines (not present in retrieved corpus). (ekpa2023areviewof pages 2-3)
Not assessed in the retrieved evidence set.
Not assessed in the retrieved evidence set.
1) Classification shift to genomics/transcriptomics: ICC and WHO‑HAEM5 explicitly expand genetically and expression-defined entities (including formerly “B‑other”) to improve risk stratification and treatment selection. (duffield2023internationalconsensusclassification pages 1-3, kansal2023diagnosisandmolecular pages 5-7)
2) MRD as a decision engine: ELN 2024 formalizes MRD timing and threshold concepts (commonly 10−4) and embeds MRD into transplant and immunotherapy decisions. (gokbuget2024managementofall pages 6-6, gokbuget2024managementofall pages 1-2)
3) Frontline immunotherapy integration and chemotherapy de-escalation: 2024 trials and reviews show movement of blinatumomab into upfront settings and successful chemo-free Ph+ strategies with high molecular response rates and reduced HSCT utilization. (lu2024reduceddosechemotherapyand pages 1-2, kantarjian2024resultsofthe pages 1-3, sebastian2024howitreat pages 1-2)
The relationship between UVR and ALL incidence reported in the 2024 British Journal of Cancer SEER ecological analysis is visually summarized in the retrieved figure. (little2024solarultravioletradiation media 5ae23b8e)
References
(shah2024acutelymphoblasticleukemia pages 1-2): Bijal Shah, Ryan J. Mattison, Ramzi Abboud, Peter Abdelmessieh, Ibrahim Aldoss, Patrick W. Burke, Daniel J. DeAngelo, Shira Dinner, Amir T. Fathi, Jordan Gauthier, Michael Haddadin, Nitin Jain, Brian Jonas, Suzanne Kirby, Michaela Liedtke, Mark Litzow, Aaron Logan, Meixiao Long, Selina Luger, James K. Mangan, Stephanie Massaro, William May, Olalekan Oluwole, Jae Park, Amanda Przespolewski, Sravanti Rangaraju, Caner Saygin, Marc Schwartz, Paul Shami, Benjamin Tomlinson, Jonathan Webster, Ajibola Awotiwon, and Katie Stehman. Acute lymphoblastic leukemia, version 2.2024, nccn clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network : JNCCN, 22 8:563-576, Oct 2024. URL: https://doi.org/10.6004/jnccn.2024.0051, doi:10.6004/jnccn.2024.0051. This article has 75 citations.
(duffield2023internationalconsensusclassification pages 1-3): Amy S. Duffield, Charles G. Mullighan, and Michael J. Borowitz. International consensus classification of acute lymphoblastic leukemia/lymphoma. Virchows Archiv, 482:11-26, Nov 2023. URL: https://doi.org/10.1007/s00428-022-03448-8, doi:10.1007/s00428-022-03448-8. This article has 226 citations and is from a peer-reviewed journal.
(kansal2023diagnosisandmolecular pages 1-2): Rina Kansal. Diagnosis and molecular pathology of lymphoblastic leukemias and lymphomas in the era of genomics and precision medicine: historical evolution and current concepts—part 2: b-/t-cell acute lymphoblastic leukemias. Lymphatics, 1:118-154, Jul 2023. URL: https://doi.org/10.3390/lymphatics1020011, doi:10.3390/lymphatics1020011. This article has 12 citations.
(kansal2023diagnosisandmolecular pages 5-7): Rina Kansal. Diagnosis and molecular pathology of lymphoblastic leukemias and lymphomas in the era of genomics and precision medicine: historical evolution and current concepts—part 2: b-/t-cell acute lymphoblastic leukemias. Lymphatics, 1:118-154, Jul 2023. URL: https://doi.org/10.3390/lymphatics1020011, doi:10.3390/lymphatics1020011. This article has 12 citations.
(yoon2024diagnosticandtherapeutic pages 1-2): Jae-Ho Yoon and Seok Lee. Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy. The Korean Journal of Internal Medicine, 39:34-56, Jan 2024. URL: https://doi.org/10.3904/kjim.2023.407, doi:10.3904/kjim.2023.407. This article has 12 citations and is from a peer-reviewed journal.
(kansal2023diagnosisandmolecular pages 4-5): Rina Kansal. Diagnosis and molecular pathology of lymphoblastic leukemias and lymphomas in the era of genomics and precision medicine: historical evolution and current concepts—part 2: b-/t-cell acute lymphoblastic leukemias. Lymphatics, 1:118-154, Jul 2023. URL: https://doi.org/10.3390/lymphatics1020011, doi:10.3390/lymphatics1020011. This article has 12 citations.
(gokbuget2024managementofall pages 1-2): Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Hervé Dombret, Michael Doubek, Adele Fielding, Robin Foà, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver Ottmann, Anita Rijneveld, Philippe Rousselot, Josep Ribera, and Renato Bassan. Management of all in adults: 2024 eln recommendations from a european expert panel. Blood, 143:1903-1930, May 2024. URL: https://doi.org/10.1182/blood.2023023568, doi:10.1182/blood.2023023568. This article has 133 citations and is from a highest quality peer-reviewed journal.
(liu2024epidemiologicalcharacteristicsand pages 1-3): Shuojie Liu, Bin Hu, and Jiaqin Zhang. Epidemiological characteristics and influencing factors of acute leukemia in children and adolescents and adults: a large population-based study. Hematology, Apr 2024. URL: https://doi.org/10.1080/16078454.2024.2327916, doi:10.1080/16078454.2024.2327916. This article has 19 citations and is from a peer-reviewed journal.
(lu2024reduceddosechemotherapyand pages 1-2): Jing Lu, Huiying Qiu, Ying Wang, Xin Zhou, Haiping Dai, Xuzhang Lu, Xiaofei Yang, Bin Gu, Ming Hong, Miao Miao, Ruinan Lu, Jun Wang, Qian Wu, Mengxing Xue, Yun Wang, Ailing Deng, Yaoyao Shen, Yin Liu, Xueqing Dou, Yutian Lei, Depei Wu, Yu Zhu, and Suning Chen. Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed ph-negative b-cell precursor acute lymphoblastic leukemia: a phase 2 trial. Journal of Hematology & Oncology, Sep 2024. URL: https://doi.org/10.1186/s13045-024-01597-8, doi:10.1186/s13045-024-01597-8. This article has 17 citations and is from a domain leading peer-reviewed journal.
(kantarjian2024resultsofthe pages 1-3): Hagop Kantarjian, Nicholas J. Short, Fadi G. Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M. Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C. Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, and Elias Jabbour. Results of the simultaneous combination of ponatinib and blinatumomab in philadelphia chromosome-positive all. Journal of Clinical Oncology, 42:4246-4251, Dec 2024. URL: https://doi.org/10.1200/jco.24.00272, doi:10.1200/jco.24.00272. This article has 80 citations and is from a highest quality peer-reviewed journal.
(ekpa2023areviewof pages 2-3): Queen L Ekpa, Prince C Akahara, Alexis M Anderson, Omowunmi O Adekoya, Olamide O Ajayi, Peace O Alabi, Okelue E Okobi, Oluwadamilola Jaiyeola, and Medara S Ekanem. A review of acute lymphocytic leukemia (all) in the pediatric population: evaluating current trends and changes in guidelines in the past decade. Cureus, Dec 2023. URL: https://doi.org/10.7759/cureus.49930, doi:10.7759/cureus.49930. This article has 49 citations.
(little2024solarultravioletradiation pages 1-2): Mark P. Little, Jim Z. Mai, Michelle Fang, Pavel Chernyavskiy, Victoria Kennerley, Elizabeth K. Cahoon, Myles G. Cockburn, Gerald M. Kendall, and Michael G. Kimlin. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-hodgkin lymphoma in a us population-based dataset. British Journal of Cancer, 130:1441-1452, Feb 2024. URL: https://doi.org/10.1038/s41416-024-02629-3, doi:10.1038/s41416-024-02629-3. This article has 15 citations and is from a domain leading peer-reviewed journal.
(little2024solarultravioletradiation pages 8-9): Mark P. Little, Jim Z. Mai, Michelle Fang, Pavel Chernyavskiy, Victoria Kennerley, Elizabeth K. Cahoon, Myles G. Cockburn, Gerald M. Kendall, and Michael G. Kimlin. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-hodgkin lymphoma in a us population-based dataset. British Journal of Cancer, 130:1441-1452, Feb 2024. URL: https://doi.org/10.1038/s41416-024-02629-3, doi:10.1038/s41416-024-02629-3. This article has 15 citations and is from a domain leading peer-reviewed journal.
(little2024solarultravioletradiation media 5ae23b8e): Mark P. Little, Jim Z. Mai, Michelle Fang, Pavel Chernyavskiy, Victoria Kennerley, Elizabeth K. Cahoon, Myles G. Cockburn, Gerald M. Kendall, and Michael G. Kimlin. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-hodgkin lymphoma in a us population-based dataset. British Journal of Cancer, 130:1441-1452, Feb 2024. URL: https://doi.org/10.1038/s41416-024-02629-3, doi:10.1038/s41416-024-02629-3. This article has 15 citations and is from a domain leading peer-reviewed journal.
(johnston2024socioeconomicdeterminantsof pages 1-2): Hannah Johnston, Hamed Rahmani Youshanlouei, Clinton Osei, Anand A. Patel, Adam DuVall, Peng Wang, Pankhuri Wanjari, Jeremy Segal, Girish Venkataraman, Jason X. Cheng, Sandeep Gurbuxani, Angela Lager, Carrie Fitzpatrick, Michael Thirman, Mariam Nawas, Hongtao Liu, Michael Drazer, Olatoyosi Odenike, Richard Larson, Wendy Stock, and Caner Saygin. Socioeconomic determinants of the biology and outcomes of acute lymphoblastic leukemia in adults. Blood Advances, 8:164-171, Dec 2024. URL: https://doi.org/10.1182/bloodadvances.2023011862, doi:10.1182/bloodadvances.2023011862. This article has 11 citations and is from a peer-reviewed journal.
(karim2023diagnosticclueof pages 2-4): MA Karim, N Yesmin, and M Begum. Diagnostic clue of acute lymphoblastic leukemia for frontline clinicians from clinicopathological features: study of 223 cases of in a tertiary care hospital from …. Unknown journal, 2023.
(talukder2024acutelymphoblasticleukemia pages 1-3): Manik Kumar Talukder, Kamrul Laila, Md. Arif Hossain, Md. Shafiqul Islam, Md. Zahidul Islam, Kalyan Benjamin Gomes, Mujammel Haque, Md. Mahbubul Islam, and Md. Imnul Islam. Acute lymphoblastic leukemia presenting as systemic juvenile idiopathic arthritis: experience from bangladesh. Open Journal of Rheumatology and Autoimmune Diseases, 14:1-12, Jan 2024. URL: https://doi.org/10.4236/ojra.2024.141001, doi:10.4236/ojra.2024.141001. This article has 1 citations.
(karim2023diagnosticclueof pages 5-6): MA Karim, N Yesmin, and M Begum. Diagnostic clue of acute lymphoblastic leukemia for frontline clinicians from clinicopathological features: study of 223 cases of in a tertiary care hospital from …. Unknown journal, 2023.
(karim2023diagnosticclueof pages 1-2): MA Karim, N Yesmin, and M Begum. Diagnostic clue of acute lymphoblastic leukemia for frontline clinicians from clinicopathological features: study of 223 cases of in a tertiary care hospital from …. Unknown journal, 2023.
(little2024solarultravioletradiation pages 11-11): Mark P. Little, Jim Z. Mai, Michelle Fang, Pavel Chernyavskiy, Victoria Kennerley, Elizabeth K. Cahoon, Myles G. Cockburn, Gerald M. Kendall, and Michael G. Kimlin. Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-hodgkin lymphoma in a us population-based dataset. British Journal of Cancer, 130:1441-1452, Feb 2024. URL: https://doi.org/10.1038/s41416-024-02629-3, doi:10.1038/s41416-024-02629-3. This article has 15 citations and is from a domain leading peer-reviewed journal.
(kantarjian2024ponatinib‐reviewofhistorical pages 10-11): Hagop M. Kantarjian, Helen T. Chifotides, Fadi G. Haddad, Nicholas J. Short, Sanam Loghavi, and Elias Jabbour. Ponatinib‐review of historical development, current status, and future research. American Journal of Hematology, 99:1576-1585, May 2024. URL: https://doi.org/10.1002/ajh.27355, doi:10.1002/ajh.27355. This article has 25 citations and is from a domain leading peer-reviewed journal.
(gokbuget2024managementofall pages 6-6): Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Hervé Dombret, Michael Doubek, Adele Fielding, Robin Foà, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver Ottmann, Anita Rijneveld, Philippe Rousselot, Josep Ribera, and Renato Bassan. Management of all in adults: 2024 eln recommendations from a european expert panel. Blood, 143:1903-1930, May 2024. URL: https://doi.org/10.1182/blood.2023023568, doi:10.1182/blood.2023023568. This article has 133 citations and is from a highest quality peer-reviewed journal.
(sebastian2024howitreat pages 1-2): Giebel Sebastian. How i treat newly diagnosed acute lymphoblastic leukemia. Clinical Hematology International, 6:51-61, May 2024. URL: https://doi.org/10.46989/001c.117026, doi:10.46989/001c.117026. This article has 8 citations.
(yoon2024diagnosticandtherapeutic pages 6-8): Jae-Ho Yoon and Seok Lee. Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy. The Korean Journal of Internal Medicine, 39:34-56, Jan 2024. URL: https://doi.org/10.3904/kjim.2023.407, doi:10.3904/kjim.2023.407. This article has 12 citations and is from a peer-reviewed journal.
(shah2024acutelymphoblasticleukemia pages 3-5): Bijal Shah, Ryan J. Mattison, Ramzi Abboud, Peter Abdelmessieh, Ibrahim Aldoss, Patrick W. Burke, Daniel J. DeAngelo, Shira Dinner, Amir T. Fathi, Jordan Gauthier, Michael Haddadin, Nitin Jain, Brian Jonas, Suzanne Kirby, Michaela Liedtke, Mark Litzow, Aaron Logan, Meixiao Long, Selina Luger, James K. Mangan, Stephanie Massaro, William May, Olalekan Oluwole, Jae Park, Amanda Przespolewski, Sravanti Rangaraju, Caner Saygin, Marc Schwartz, Paul Shami, Benjamin Tomlinson, Jonathan Webster, Ajibola Awotiwon, and Katie Stehman. Acute lymphoblastic leukemia, version 2.2024, nccn clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network : JNCCN, 22 8:563-576, Oct 2024. URL: https://doi.org/10.6004/jnccn.2024.0051, doi:10.6004/jnccn.2024.0051. This article has 75 citations.
(ghosh2024incidenceandsurvivability pages 1-3): Ishan Ghosh and Sudipto Mukherjee. Incidence and survivability of acute lymphocytic leukemia patients in the united states: analysis of seer data set from 2000-2019. Journal of Cancer Therapy, 15:141-163, Jan 2024. URL: https://doi.org/10.4236/jct.2024.154014, doi:10.4236/jct.2024.154014. This article has 0 citations.
(stelljes2024ph−allimmunotherapy pages 1-2): Matthias Stelljes. Ph− all: immunotherapy in upfront treatment. Hematology, 2024:86-92, Dec 2024. URL: https://doi.org/10.1182/hematology.2024000531, doi:10.1182/hematology.2024000531. This article has 1 citations and is from a peer-reviewed journal.
(sebastian2024howitreat pages 5-7): Giebel Sebastian. How i treat newly diagnosed acute lymphoblastic leukemia. Clinical Hematology International, 6:51-61, May 2024. URL: https://doi.org/10.46989/001c.117026, doi:10.46989/001c.117026. This article has 8 citations.
(kantarjian2024inotuzumabozogamicinin pages 15-17): Hagop M. Kantarjian, Nicolas Boissel, Cristina Papayannidis, Marlise R. Luskin, Matthias Stelljes, Anjali S. Advani, Elias J. Jabbour, Josep‐Maria Ribera, and David I. Marks. Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: development, current status, and future directions. Cancer, 130:3631-3646, Aug 2024. URL: https://doi.org/10.1002/cncr.35505, doi:10.1002/cncr.35505. This article has 16 citations and is from a domain leading peer-reviewed journal.
(gokbuget2024managementofall pages 21-22): Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Hervé Dombret, Michael Doubek, Adele Fielding, Robin Foà, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver Ottmann, Anita Rijneveld, Philippe Rousselot, Josep Ribera, and Renato Bassan. Management of all in adults: 2024 eln recommendations from a european expert panel. Blood, 143:1903-1930, May 2024. URL: https://doi.org/10.1182/blood.2023023568, doi:10.1182/blood.2023023568. This article has 133 citations and is from a highest quality peer-reviewed journal.
(kantarjian2024resultsofthe pages 3-4): Hagop Kantarjian, Nicholas J. Short, Fadi G. Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M. Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C. Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, and Elias Jabbour. Results of the simultaneous combination of ponatinib and blinatumomab in philadelphia chromosome-positive all. Journal of Clinical Oncology, 42:4246-4251, Dec 2024. URL: https://doi.org/10.1200/jco.24.00272, doi:10.1200/jco.24.00272. This article has 80 citations and is from a highest quality peer-reviewed journal.
(graiqevciuka2024implementationofpharmacogenetics pages 5-7): Violeta Graiqevci-Uka, Emir Behluli, Rifat Hadziselimovic, Thomas Liehr, and Gazmend Temaj. Implementation of pharmacogenetics for treatment of patients with acute lymphoblastic leukemia. Research Results in Pharmacology, 10:27-39, Jun 2024. URL: https://doi.org/10.18413/rrpharmacology.10.382, doi:10.18413/rrpharmacology.10.382. This article has 2 citations.
(graiqevciuka2024implementationofpharmacogenetics pages 1-3): Violeta Graiqevci-Uka, Emir Behluli, Rifat Hadziselimovic, Thomas Liehr, and Gazmend Temaj. Implementation of pharmacogenetics for treatment of patients with acute lymphoblastic leukemia. Research Results in Pharmacology, 10:27-39, Jun 2024. URL: https://doi.org/10.18413/rrpharmacology.10.382, doi:10.18413/rrpharmacology.10.382. This article has 2 citations.
just research-disorder asta Acute_Lymphoblastic_Leukemia
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The accepted disease model for ALL is a multi-step transformation in which a founding cytogenetic lesion (translocation creating a chimeric oncogene or aneuploidy) is acquired in a B- or T-lymphoid progenitor — often in utero in B-ALL — followed by acquisition of cooperating mutations that: - corrupt lymphoid transcriptional programs (chimeric TFs; KMT2A-driven HOXA upregulation; NOTCH1 in T-ALL) - block differentiation (IKZF1, PAX5, EBF1 lesions in B-ALL; CDKN2A/B loss most prominent in T-ALL) - drive constitutive proliferation/survival signaling (BCR-ABL1 RAS/PI3K/JAK, NOTCH1-MYC, KMT2A-HOXA9/MEIS1)
The clonal lymphoblast population then expands in the marrow and disseminates to extramedullary sites, producing two dominant clinical axes: 1. Bone marrow failure with pancytopenia (anemia, bleeding from thrombocytopenia, infections from neutropenia) 2. Extramedullary disease (lymphadenopathy, hepatosplenomegaly, anterior mediastinal mass in T-ALL, CNS infiltration as a sanctuary site).
Risk stratification, treatment choice (TKIs in Ph+ and Ph-like ALL, JAK inhibitors in CRLF2-rearranged disease, blinatumomab/inotuzumab/CAR-T in relapsed B-ALL, allogeneic HSCT for highest-risk groups), and prognosis are governed largely by molecular subtype and MRD response.
Curated subtypes in the YAML: - B-ALL with ETV6-RUNX1 (favorable) - B-ALL with TCF3-PBX1 (intermediate, historical CNS relapse risk) - B-ALL with KMT2A rearrangement (high-risk; infant-predominant) - Ph+ ALL (BCR-ABL1) (TKI-targetable) - Ph-like ALL (BCR-ABL1-like) (high-risk; kinase-rearranged; partly TKI/JAK-targetable) - T-ALL (NOTCH1-driven; mediastinal mass; ETP-ALL subset)
genetic entry was given a single canonical gene_term (the
more clinically central partner: ABL1 for BCR-ABL1, RUNX1 for ETV6-RUNX1,
PBX1 for TCF3-PBX1). The gene_term slot is single-valued, so the second
partner is documented inline in notes with its hgnc: ID for traceability.