early T cell progenitor acute lymphoblastic leukemia

Summary

early T cell progenitor acute lymphoblastic leukemia (MONDO:0100291) is a cancer with 4 cohort genes (4 CIViC-evidence somatic drivers; 4 ClinVar predisposition records) and 3 clinical trials. Top therapeutic interventions include daunorubicin, cyclophosphamide anhydrous, and omacetaxine mepesuccinate.

At a glance

• Classification: Cancer
• Cohort genes: 4
• ClinVar variants: 4
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	early T cell progenitor acute lymphoblastic leukemia
Mondo ID	MONDO:0100291
NCIT	C130043
UMLS	C4329780
MedGen	1385175
GARD	0026127
Is cancer (heuristic)	yes

Also known as: early T acute lymphoblastic leukaemia · early T acute lymphoblastic leukemia · early T-cell precursor acute lymphoblastic leukaemia · early T-cell precursor acute lymphoblastic leukemia · early T-cell precursor lymphoblastic leukaemia · early T-cell precursor lymphoblastic leukemia · ETP ALL · ETP-ALL

Data availability: 4 ClinVar variants · 1 cell line.

Disease family

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › hematopoietic and lymphoid cell neoplasm › lymphoid neoplasm › precursor lymphoblastic lymphoma/leukemia › acute lymphoblastic leukemia › T-cell acute lymphoblastic leukemia › early T cell progenitor acute lymphoblastic leukemia

Related subtypes (3): T-cell childhood acute lymphocytic leukemia, T-cell prolymphocytic leukemia, aggressive NK-cell leukemia

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
208339	NM_000760.4(CSF3R):c.1853C>T (p.Thr618Ile)	CSF3R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208338	NM_022552.5(DNMT3A):c.1204C>T (p.Gln402Ter)	DNMT3A	Pathogenic	no assertion criteria provided
208337	NM_017617.5(NOTCH1):c.4775T>G (p.Phe1592Cys)	NOTCH1	Pathogenic	no assertion criteria provided
13335	NM_002834.5(PTPN11):c.854T>C (p.Phe285Ser)	PTPN11	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CSF3R	LoF	AML,BLADDER,HNSC	CIViC #1239
DNMT3A	LoF	AML,BRCA,CCRCC,HCC,LGGNOS,MDS,PCM,PRCC,WDTC	CIViC #18
NOTCH1	LoF	ALL,ANGS,BCC,BLCA,BRCA,CESC,CHOL,CLLSLL,CSCC,DLBCLNOS,ESCA,HNSC,LGGNOS,LUAD,LUSC,MBL,MEL,MGCT,NPC,NSCLC,OVT,READ,SACA,SCLC,SKIN,VULVA	CIViC #50
PTPN11	Act	ALL,AML,CLLSLL,COADREAD,GBM,LGGNOS,NBL,PAST,PCM	CIViC #4685

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSF3R	Orphanet:279943	Hereditary neutrophilia
CSF3R	Orphanet:420702	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency
CSF3R	Orphanet:86829	Chronic neutrophilic leukemia
CSF3R	Orphanet:98824	Atypical chronic myeloid leukemia
DNMT3A	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
DNMT3A	Orphanet:404443	Tatton-Brown-Rahman syndrome
DNMT3A	Orphanet:658595	DNMT3A-related microcephalic dwarfism
DNMT3A	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome
PTPN11	Orphanet:2499	Metachondromatosis
PTPN11	Orphanet:500	Noonan syndrome with multiple lentigines
PTPN11	Orphanet:648	Noonan syndrome
PTPN11	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CSF3R	HGNC:2439	ENSG00000119535	Q99062	Granulocyte colony-stimulating factor receptor	clinvar
DNMT3A	HGNC:2978	ENSG00000119772	Q9Y6K1	DNA (cytosine-5)-methyltransferase 3A	clinvar
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF3R	Granulocyte colony-stimulating factor receptor	Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation.
DNMT3A	DNA (cytosine-5)-methyltransferase 3A	Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.75

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
Complement	1	67.0×	0.059
Phosphatase	1	21.0×	0.094
Antibody/Immunoglobulin	1	7.3×	0.174
Scaffold/PPI	1	4.3×	0.212

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSF3R	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd
DNMT3A	Complement	yes	2.1.1.37	PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
blood	1
granulocyte	1
monocyte	1
ganglionic eminence	1
sural nerve	1
colonic epithelium	1
visceral pleura	1
dorsal motor nucleus of vagus nerve	1
globus pallidus	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF3R	192	broad	marker	granulocyte, monocyte, blood
DNMT3A	223	ubiquitous	marker	sural nerve, ganglionic eminence, ventricular zone
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
PTPN11	295	ubiquitous	marker	medial globus pallidus, dorsal motor nucleus of vagus nerve, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH1	7,411
PTPN11	6,009
DNMT3A	4,771
CSF3R	3,315

Structural data

PDB: 4 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN11	Q06124	115
DNMT3A	Q9Y6K1	43
NOTCH1	P46531	29
CSF3R	Q99062	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 84. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by CSF3 (G-CSF)	2	285.5×	0.001	CSF3R, PTPN11
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	571.0×	0.015	NOTCH1
Defective LFNG causes SCDO3	1	571.0×	0.015	NOTCH1
MET activates PTPN11	1	571.0×	0.015	PTPN11
Co-inhibition by BTLA	1	571.0×	0.015	PTPN11
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	475.8×	0.015	NOTCH1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	407.9×	0.015	NOTCH1
STAT5 Activation	1	407.9×	0.015	PTPN11
Regulation of NFE2L2 gene expression	1	356.9×	0.015	NOTCH1
Netrin mediated repulsion signals	1	317.2×	0.015	PTPN11
MAPK1 (ERK2) activation	1	285.5×	0.015	PTPN11
STAT5 activation downstream of FLT3 ITD mutants	1	285.5×	0.015	PTPN11
MAPK3 (ERK1) activation	1	259.6×	0.015	PTPN11
Signaling by Leptin	1	259.6×	0.015	PTPN11
Interleukin-6 signaling	1	237.9×	0.015	PTPN11
Activated NTRK2 signals through FRS2 and FRS3	1	237.9×	0.015	PTPN11
NFE2L2 regulating tumorigenic genes	1	237.9×	0.015	NOTCH1
PECAM1 interactions	1	219.6×	0.015	PTPN11
Regulation of IFNG signaling	1	203.9×	0.015	PTPN11
RUNX3 regulates NOTCH signaling	1	203.9×	0.015	NOTCH1
Prolactin receptor signaling	1	190.3×	0.015	PTPN11
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	190.3×	0.015	NOTCH1
Signaling by FLT3 ITD and TKD mutants	1	190.3×	0.015	PTPN11
Spry regulation of FGF signaling	1	178.4×	0.015	PTPN11
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	178.4×	0.015	NOTCH1
Signal regulatory protein family interactions	1	167.9×	0.015	PTPN11
Platelet sensitization by LDL	1	167.9×	0.015	PTPN11
SUMOylation of DNA methylation proteins	1	167.9×	0.015	DNMT3A
Regulation of RUNX1 Expression and Activity	1	167.9×	0.015	PTPN11
GAB1 signalosome	1	158.6×	0.015	PTPN11

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
coronary sinus valve morphogenesis	1	4213.0×	0.005	NOTCH1
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	4213.0×	0.005	NOTCH1
foregut morphogenesis	1	4213.0×	0.005	NOTCH1
negative regulation of cortisol secretion	1	4213.0×	0.005	PTPN11
negative regulation of growth hormone secretion	1	4213.0×	0.005	PTPN11
regulation of epithelial cell proliferation involved in prostate gland development	1	4213.0×	0.005	NOTCH1
venous endothelial cell differentiation	1	4213.0×	0.005	NOTCH1
endocardium morphogenesis	1	2106.5×	0.005	NOTCH1
coronary vein morphogenesis	1	2106.5×	0.005	NOTCH1
cardiac right atrium morphogenesis	1	2106.5×	0.005	NOTCH1
growth involved in heart morphogenesis	1	2106.5×	0.005	NOTCH1
obsolete negative regulation of cell proliferation involved in heart valve morphogenesis	1	2106.5×	0.005	NOTCH1
cell differentiation in spinal cord	1	2106.5×	0.005	NOTCH1
microvillus organization	1	2106.5×	0.005	PTPN11
intestinal epithelial cell migration	1	2106.5×	0.005	PTPN11
positive regulation of aorta morphogenesis	1	2106.5×	0.005	NOTCH1
mitral valve formation	1	1404.3×	0.005	NOTCH1
cardiac chamber formation	1	1404.3×	0.005	NOTCH1
auditory receptor cell fate commitment	1	1404.3×	0.005	NOTCH1
cerebellar cortex formation	1	1404.3×	0.005	PTPN11
retinal cone cell differentiation	1	1404.3×	0.005	NOTCH1
secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development	1	1404.3×	0.005	NOTCH1
cardiac vascular smooth muscle cell development	1	1404.3×	0.005	NOTCH1
vasculogenesis involved in coronary vascular morphogenesis	1	1404.3×	0.005	NOTCH1
regulation of cell adhesion involved in heart morphogenesis	1	1404.3×	0.005	NOTCH1
distal tubule development	1	1404.3×	0.005	NOTCH1
chemical synaptic transmission, postsynaptic	1	1404.3×	0.005	NOTCH1
positive regulation of cellular response to hypoxia	1	1404.3×	0.005	DNMT3A
apoptotic process involved in embryonic digit morphogenesis	1	1404.3×	0.005	NOTCH1
positive regulation of apoptotic process involved in morphogenesis	1	1404.3×	0.005	NOTCH1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 2

Druggability breadth: 4 of 4 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PTPN11	8	4
NOTCH1	1	2
CSF3R	0	0
DNMT3A	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ESTRAMUSTINE PHOSPHATE	4	PTPN11
VAREGACESTAT	2	NOTCH1
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PTPN11	588	Binding:585, Functional:2, ADMET:1
DNMT3A	120	Binding:118, ADMET:1, Functional:1
NOTCH1	23	Binding:19, ADMET:4
CSF3R	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DNMT3A	120
PTPN11	588

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

9 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.

Compound	Max phase	Cohort target (bioactivity)
ESTRAMUSTINE PHOSPHATE	4	PTPN11
VAREGACESTAT	2	NOTCH1
ENOXOLONE	2	PTPN11
CEFSULODIN	2	PTPN11
BATOPROTAFIB	2	PTPN11
VOCIPROTAFIB	2	PTPN11
JAB-3068	1	PTPN11
PF-07284892	1	PTPN11
BBP-398	1	PTPN11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PTPN11
B	Phased (≥1) drug, not yet approved	1	NOTCH1
C	Druggable family + PDB, no drug	2	CSF3R, DNMT3A
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNMT3A	120	—
CSF3R	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06361329	PHASE3	RECRUITING	Comparing the Efficacy of VHAG and Traditional Chemotherapy Regimens in Newly Diagnosed ETP-ALL
NCT07012447	PHASE2	RECRUITING	Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations
NCT04582487	Not specified	UNKNOWN	Advancing Chemical and Genomic Strategies for Relapsed/Refractory T-ALL and ETP-ALL

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DAUNORUBICIN	4	2
CYCLOPHOSPHAMIDE ANHYDROUS	4	1
OMACETAXINE MEPESUCCINATE	4	1
VENETOCLAX	4	1
VINDESINE	4	1
CHEMBL3774735	0	1
CHEMBL3970001	0	1