B-cell childhood acute lymphoblastic leukemia

Summary

B-cell childhood acute lymphoblastic leukemia (MONDO:0000872) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 2 ClinVar predisposition records) and 96 clinical trials. Top therapeutic interventions include mercaptopurine anhydrous, pegaspargase, and blinatumomab.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	B-cell childhood acute lymphoblastic leukemia
Mondo ID	MONDO:0000872
EFO	EFO:1001946
DOID	DOID:0080146
NCIT	C9140
UMLS	C0279584
MedGen	83526
GARD	0022835
Is cancer (heuristic)	yes

Also known as: B acute lymphoblastic leukaemia · B acute lymphoblastic leukemia · B cell childhood acute lymphoblastic leukaemia · B cell childhood acute lymphoblastic leukemia · B cell childhood acute lymphocytic leukaemia · B cell childhood acute lymphocytic leukemia · B cell childhood ALL · B cell paediatric acute lymphoblastic leukaemia · B cell paediatric acute lymphocytic leukaemia · B cell paediatric ALL · B cell pediatric acute lymphoblastic leukemia · B cell pediatric acute lymphocytic leukemia · B cell pediatric ALL · B-cell childhood acute lymphocytic leukaemia · B-cell childhood acute lymphocytic leukemia · B-cell childhood acute lymphogenous leukaemia · B-cell childhood acute lymphogenous leukemia · B-cell childhood acute lymphoid leukaemia · B-cell childhood acute lymphoid leukemia · B-cell childhood ALL (+15 more)

Data availability: 2 ClinVar variants · 228 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › immune system cancer › B-cell childhood acute lymphoblastic leukemia

Related subtypes (24): lymphatic system cancer, T-cell childhood acute lymphocytic leukemia, primary central nervous system lymphoma, thymus cancer, solitary plasmacytoma of chest wall, dendritic cell sarcoma, Waldeyer’s ring cancer, breast diffuse large B-cell lymphoma, colon Burkitt lymphoma, colorectal diffuse large B-cell lymphoma, gastric mantle cell lymphoma, liver diffuse large B-cell lymphoma, primary pulmonary diffuse large B-cell lymphoma, small intestinal Burkitt lymphoma, small intestinal diffuse large B-cell lymphoma, small intestinal enteropathy-associated T-cell lymphoma, thyroid gland diffuse large B-cell lymphoma, plasma cell myeloma, indolent primary cutaneous B-cell lymphoma, systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood, mast cell sarcoma, subcutaneous panniculitis-like T-cell lymphoma, bone marrow cancer, primary vitreoretinal large b-cell lymphoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1223371	NM_001002295.2(GATA3):c.779-1748C>A	GATA3	Benign	criteria provided, multiple submitters, no conflicts
3893658	NM_001002295.2(GATA3):c.778+1123T>C	GATA3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
GATA3	Act	ALL,BRCA	CIViC #2189

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GATA3	Orphanet:2237	Hypoparathyroidism-sensorineural deafness-renal disease syndrome
GATA3	Orphanet:585936	B-lymphoblastic leukemia/lymphoma with hyperdiploidy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GATA3	HGNC:4172	ENSG00000107485	P23771	Trans-acting T-cell-specific transcription factor GATA-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GATA3	Trans-acting T-cell-specific transcription factor GATA-3	Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GATA3	Transcription factor	no		Znf_GATA, Znf_NHR/GATA, TF_GATA-2/3

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
endometrium epithelium	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GATA3	220	broad	marker	upper leg skin, skin of hip, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GATA3	5,990

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GATA3	P23771	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.006	GATA3
Formation of the nephric duct	1	634.4×	0.006	GATA3
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.017	GATA3
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.017	GATA3
RUNX1 regulates transcription of genes involved in differentiation of HSCs	1	95.2×	0.017	GATA3
Estrogen-dependent gene expression	1	75.6×	0.017	GATA3
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.017	GATA3
Ub-specific processing proteases	1	53.1×	0.019	GATA3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
type IV hypersensitivity	1	16852.0×	0.001	GATA3
obsolete negative regulation of cell proliferation involved in mesonephros development	1	16852.0×	0.001	GATA3
regulation of cellular response to X-ray	1	16852.0×	0.001	GATA3
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation	1	16852.0×	0.001	GATA3
obsolete negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation	1	16852.0×	0.001	GATA3
pro-T cell differentiation	1	8426.0×	0.002	GATA3
parathyroid hormone secretion	1	8426.0×	0.002	GATA3
regulation of nephron tubule epithelial cell differentiation	1	8426.0×	0.002	GATA3
thymic T cell selection	1	5617.3×	0.002	GATA3
nephric duct formation	1	5617.3×	0.002	GATA3
immune system development	1	4213.0×	0.002	GATA3
ureter maturation	1	4213.0×	0.002	GATA3
regulation of T-helper cell differentiation	1	4213.0×	0.002	GATA3
mast cell differentiation	1	4213.0×	0.002	GATA3
positive regulation of thyroid hormone generation	1	4213.0×	0.002	GATA3
negative regulation of mammary gland epithelial cell proliferation	1	3370.4×	0.002	GATA3
nephric duct morphogenesis	1	3370.4×	0.002	GATA3
otic vesicle development	1	2808.7×	0.002	GATA3
positive regulation of ureteric bud formation	1	2808.7×	0.002	GATA3
parathyroid gland development	1	2407.4×	0.002	GATA3
ureteric bud formation	1	2407.4×	0.002	GATA3
lymphocyte migration	1	2407.4×	0.002	GATA3
norepinephrine biosynthetic process	1	2106.5×	0.002	GATA3
ureter morphogenesis	1	2106.5×	0.002	GATA3
positive regulation of transcription regulatory region DNA binding	1	2106.5×	0.002	GATA3
regulation of epithelial cell differentiation	1	1872.4×	0.002	GATA3
T-helper 2 cell differentiation	1	1872.4×	0.002	GATA3
anatomical structure formation involved in morphogenesis	1	1872.4×	0.002	GATA3
mesonephros development	1	1532.0×	0.002	GATA3
cellular response to interferon-alpha	1	1532.0×	0.002	GATA3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GATA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GATA3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GATA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 96.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	29
PHASE1	25
PHASE1/PHASE2	15
PHASE3	13
Not specified	9
PHASE4	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01990807	PHASE4	UNKNOWN	Treatment Protocol of Children With Philadelphia Chromosome Negative High Risk Acute Lymphoblastic Leukemia
NCT02618109	PHASE4	TERMINATED	Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia
NCT02101853	PHASE3	ACTIVE_NOT_RECRUITING	Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
NCT03007147	PHASE3	ACTIVE_NOT_RECRUITING	Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
NCT03150693	PHASE3	RECRUITING	Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia
NCT03914625	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
NCT03937544	PHASE2/PHASE3	RECRUITING	Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL
NCT03959085	PHASE3	RECRUITING	Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
NCT05602194	PHASE3	ACTIVE_NOT_RECRUITING	Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
NCT00075725	PHASE3	COMPLETED	Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
NCT00103285	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00381680	PHASE3	COMPLETED	Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
NCT00382109	PHASE3	COMPLETED	Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission
NCT00671034	PHASE3	COMPLETED	Calaspargase Pegol or Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
NCT01190930	PHASE3	COMPLETED	Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma
NCT02883049	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations
NCT01371630	PHASE1/PHASE2	RECRUITING	Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia
NCT02143414	PHASE2	ACTIVE_NOT_RECRUITING	Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia
NCT02877303	PHASE2	RECRUITING	Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia
NCT02981628	PHASE2	RECRUITING	Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
NCT03441061	PHASE2	ACTIVE_NOT_RECRUITING	Inotuzumab Ozogamicin in Treating Patients With B-cell Acute Lymphocytic Leukemia With Positive Minimal Residual Disease
NCT03504644	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Venetoclax and Vincristine in Treating Patients With Relapsed or Refractory T-cell or B-cell Acute Lymphoblastic Leukemia
NCT03739814	PHASE2	RECRUITING	Inotuzumab Ozogamicin and Blinatumomab With or Without Ponatinib in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
NCT04546399	PHASE2	RECRUITING	A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)
NCT04746209	PHASE2	RECRUITING	Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT
NCT05281809	PHASE2	RECRUITING	Local Manufacture of CAR T-Cell Products for the Treatment of B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia
NCT05303792	PHASE2	ACTIVE_NOT_RECRUITING	Testing the Combination of Inotuzumab Ozogamicin and Lower Dose Chemotherapy Compared to Usual Chemotherapy for Adults With B-Cell Acute Lymphoblastic Leukemia or B-Cell Lymphoblastic Lymphoma
NCT05310591	PHASE1/PHASE2	RECRUITING	Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence
NCT06124157	PHASE2	RECRUITING	A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
NCT06317662	PHASE2	RECRUITING	Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia
NCT06703216	PHASE1/PHASE2	NOT_YET_RECRUITING	Pre-emptive Anakinra for Cytokine Event Reduction
NCT00052520	PHASE1/PHASE2	COMPLETED	Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation
NCT00058461	PHASE2	TERMINATED	Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin’s Lymphoma or Acute Lymphoblastic Leukemia
NCT00061945	PHASE1/PHASE2	COMPLETED	Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia
NCT00867529	PHASE2	COMPLETED	Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma
NCT00873093	PHASE2	COMPLETED	Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
NCT01093586	PHASE2	COMPLETED	Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01700946	PHASE2	COMPLETED	Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma
NCT02227108	PHASE2	TERMINATED	Study in Pediatrics With Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma
NCT02420717	PHASE2	TERMINATED	Ruxolitinib Phosphate or Dasatinib With Chemotherapy in Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MERCAPTOPURINE ANHYDROUS	4	51
PEGASPARGASE	4	17
BLINATUMOMAB	4	15
THIOGUANINE	4	14
INOTUZUMAB OZOGAMICIN	4	12
FLUDARABINE PHOSPHATE	4	11
CALASPARGASE PEGOL	4	8
DAUNORUBICIN	4	8
LEUCOVORIN	4	7
ASPARAGINASE	4	6
MITOXANTRONE	4	5
ASPARAGINASE ERWINIA CHRYSANTHEMI	4	4
HYDROCORTISONE SODIUM SUCCINATE	4	4
IMATINIB	4	4
VINCRISTINE	4	4
DEXRAZOXANE	4	3
ALLOPURINOL	4	2
CLOFARABINE	4	2
DASATINIB ANHYDROUS	4	2
LEVOLEUCOVORIN	4	2
ACYCLOVIR	4	1
ALEMTUZUMAB	4	1
CYTARABINE	4	1
ETOPOSIDE PHOSPHATE	4	1
HYDROCORTISONE	4	1
IFOSFAMIDE	4	1
INTERFERON BETA-1A	4	1
LEVOCARNITINE	4	1
METHOTREXATE SODIUM	4	1
MOXETUMOMAB PASUDOTOX	4	1