T-cell acute lymphoblastic leukemia

Summary

T-cell acute lymphoblastic leukemia (MONDO:0004963) is a cancer with 7 cohort genes (7 CIViC-evidence somatic drivers; 4 ClinVar predisposition records) and 82 clinical trials. Molecularly, NOTCH1 Mutation confers sensitivity to Prednisone in T-cell Acute Lymphoblastic Leukemia (CIViC Level C); 17 further subtype–drug associations are mapped below. Top therapeutic interventions include mercaptopurine anhydrous, nelarabine, and calaspargase pegol.

At a glance

• Classification: Cancer
• Cohort genes: 7
• ClinVar variants: 4
• Clinical trials: 82
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	T-cell acute lymphoblastic leukemia
Mondo ID	MONDO:0004963
EFO	EFO:0000209
DOID	DOID:5603
NCIT	C3183
SNOMED CT	277575008
UMLS	C1961099
MedGen	368378
GARD	0024138
Is cancer (heuristic)	yes

Also known as: acute T cell leukaemia · acute T cell leukemia · acute T cell lymphoblastic leukaemia · acute T cell lymphoblastic leukemia · acute T cell lymphocytic leukaemia · acute T cell lymphocytic leukemia · acute T-cell leukaemia · acute T-cell leukemia · acute T-cell lymphoblastic leukaemia · acute T-cell lymphoblastic leukemia · acute T-cell lymphocytic leukaemia · acute T-cell lymphocytic leukemia · precursor T lymphoblastic leukaemia · precursor T-lymphoblastic leukaemia · precursor T-lymphoblastic leukaemia (T-cell ALL) · precursor T-lymphoblastic leukemia · precursor T-lymphoblastic leukemia (T-cell ALL) · T acute lymphoblastic leukaemia · T acute lymphoblastic leukemia · T-ALL (+6 more)

Data availability: 4 ClinVar variants · 8 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: human disease › 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

Related subtypes (11): childhood acute lymphoblastic leukemia, prolymphocytic leukemia, adult acute lymphoblastic leukemia, null-cell leukemia, B-cell acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, lymphoblastic leukemia, acute, with lymphomatous features, plasma cell leukemia, acute biphenotypic leukemia, precursor B-cell acute lymphoblastic leukemia, precursor T-cell acute lymphoblastic leukemia

Subtypes (4): T-cell childhood acute lymphocytic leukemia, T-cell prolymphocytic leukemia, aggressive NK-cell leukemia, early T cell progenitor acute lymphoblastic 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:

4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
617566	Single allele	ABL1	Pathogenic	no assertion criteria provided
9513	NM_138761.4(BAX):c.199G>A (p.Gly67Arg)	BAX	Pathogenic	no assertion criteria provided
9514	NM_138761.4(BAX):c.115_121del (p.Gly39fs)	BAX	Pathogenic	no assertion criteria provided
6259	NM_003921.5(BCL10):c.136dup (p.Ile46fs)	BCL10	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
DNMT3A	LoF	AML,BRCA,CCRCC,HCC,LGGNOS,MDS,PCM,PRCC,WDTC	CIViC #18
MTOR	Act	BLCA,BRCA,CCRCC,CHRCC,CLLSLL,COADREAD,HCC,LGGNOS,PANET,RCC,UCEC	CIViC #2073
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
NT5C2			CIViC #9189
ABL1	LoF	UCEC	CIViC #4
BAX			CIViC #550
BCL10	LoF	DLBCLNOS,MLYM	CIViC #7074

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
MTOR	Orphanet:269001	Isolated focal cortical dysplasia type IIa
MTOR	Orphanet:269008	Isolated focal cortical dysplasia type IIb
MTOR	Orphanet:457485	Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
MTOR	Orphanet:99802	Hemimegalencephaly
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome
NT5C2	Orphanet:320396	Autosomal recessive spastic paraplegia type 45
ABL1	Orphanet:521	Chronic myeloid leukemia
ABL1	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
ABL1	Orphanet:643503	Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome
ABL1	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
BCL10	Orphanet:52417	MALT lymphoma

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	4
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNMT3A	HGNC:2978	ENSG00000119772	Q9Y6K1	DNA (cytosine-5)-methyltransferase 3A	civic_evidence
MTOR	HGNC:3942	ENSG00000198793	P42345	Serine/threonine-protein kinase mTOR	civic_evidence
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	civic_evidence
NT5C2	HGNC:8022	ENSG00000076685	P49902	Cytosolic purine 5’-nucleotidase	civic_evidence
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	clinvar
BAX	HGNC:959	ENSG00000087088	Q07812	Apoptosis regulator BAX	clinvar
BCL10	HGNC:989	ENSG00000142867	O95999	B-cell lymphoma/leukemia 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
MTOR	Serine/threonine-protein kinase mTOR	Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals.
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.
NT5C2	Cytosolic purine 5’-nucleotidase	Broad specificity cytosolic 5’-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates.
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
BAX	Apoptosis regulator BAX	Plays a role in the mitochondrial apoptotic process.
BCL10	B-cell lymphoma/leukemia 10	Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.57

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	38.3×	0.065
Kinase	2	7.9×	0.065
Scaffold/PPI	1	2.5×	0.568
Enzyme (other)	1	1.7×	0.571
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNMT3A	Complement	yes	2.1.1.37	PWWP_dom, C5_MeTfrase, C5_DNA_meth_AS
MTOR	Kinase	yes		PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
NT5C2	Enzyme (other)	yes	3.1.3.5	HAD-SF_hydro_IG_5-nucl, Pur_nucleotidase, HAD_sf
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
BAX	Other/Unknown	no		Bcl2-like, Bcl2_BH1_motif_CS, Bcl2_BH2_motif_CS
BCL10	Other/Unknown	no		CARD, DEATH-like_dom_sf, BCL10/E10

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
ganglionic eminence	1
sural nerve	1
cerebellar hemisphere	1
primordial germ cell in gonad	1
right hemisphere of cerebellum	1
colonic epithelium	1
visceral pleura	1
buccal mucosa cell	1
oral cavity	1
parotid gland	1
frontal pole	1
middle frontal gyrus	1
paraflocculus	1
granulocyte	1
mucosa of transverse colon	1
stromal cell of endometrium	1
esophagus squamous epithelium	1
mucosa of sigmoid colon	1
squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNMT3A	223	ubiquitous	marker	sural nerve, ganglionic eminence, ventricular zone
MTOR	207	ubiquitous	marker	primordial germ cell in gonad, right hemisphere of cerebellum, cerebellar hemisphere
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
NT5C2	294	ubiquitous	marker	parotid gland, buccal mucosa cell, oral cavity
ABL1	283	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
BAX	244	ubiquitous	marker	mucosa of transverse colon, stromal cell of endometrium, granulocyte
BCL10	280	ubiquitous	marker	esophagus squamous epithelium, mucosa of sigmoid colon, squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MTOR	9,490
NOTCH1	7,411
ABL1	6,937
DNMT3A	4,771
BCL10	1,873
NT5C2	1,513
BAX	543

Structural data

PDB: 7 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABL1	P00519	85
MTOR	P42345	70
DNMT3A	Q9Y6K1	43
NT5C2	P49902	43
BAX	Q07812	37
NOTCH1	P46531	29
BCL10	O95999	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 150. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Response of endothelial cells to shear stress	2	85.9×	0.016	MTOR, ABL1
Cellular responses to mechanical stimuli	2	74.2×	0.016	MTOR, ABL1
Transcriptional regulation by RUNX2	2	72.5×	0.016	ABL1, BAX
Activation, translocation and oligomerization of BAX	1	815.7×	0.044	BAX
NTRK3 as a dependence receptor	1	543.8×	0.044	BAX
Abacavir metabolism	1	407.9×	0.044	NT5C2
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	326.3×	0.044	NOTCH1
Defective LFNG causes SCDO3	1	326.3×	0.044	NOTCH1
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	271.9×	0.044	NOTCH1
Release of apoptotic factors from the mitochondria	1	233.1×	0.044	BAX
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	233.1×	0.044	NOTCH1
Abacavir ADME	1	203.9×	0.044	NT5C2
Regulation of NFE2L2 gene expression	1	203.9×	0.044	NOTCH1
Role of ABL in ROBO-SLIT signaling	1	181.3×	0.044	ABL1
Nucleotide catabolism	1	181.3×	0.044	NT5C2
Signaling by NTRK3 (TRKC)	1	163.1×	0.044	BAX
Purine catabolism	1	148.3×	0.044	NT5C2
Ribavirin ADME	1	148.3×	0.044	NT5C2
NFE2L2 regulating tumorigenic genes	1	135.9×	0.044	NOTCH1
Apoptotic factor-mediated response	1	125.5×	0.044	BAX
Downstream signaling events of B Cell Receptor (BCR)	1	116.5×	0.044	BCL10
Protein ubiquitination	1	116.5×	0.044	BCL10
RUNX2 regulates bone development	1	116.5×	0.044	ABL1
RUNX3 regulates NOTCH signaling	1	116.5×	0.044	NOTCH1
Transcriptional Regulation by TP53	2	17.7×	0.044	MTOR, BAX
Signaling by Receptor Tyrosine Kinases	2	14.8×	0.044	MTOR, BAX
RNA Polymerase II Transcription	3	9.7×	0.044	MTOR, ABL1, BAX
Gene expression (Transcription)	3	7.7×	0.044	MTOR, ABL1, BAX
Generic Transcription Pathway	3	6.5×	0.044	MTOR, ABL1, BAX
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	108.8×	0.044	NOTCH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptotic process involved in embryonic digit morphogenesis	2	1605.0×	2e-04	NOTCH1, BAX
post-embryonic development	3	88.1×	9e-04	DNMT3A, MTOR, ABL1
B cell apoptotic process	2	401.2×	0.002	BAX, BCL10
cellular response to hypoxia	3	52.0×	0.002	DNMT3A, MTOR, NOTCH1
cardiac muscle cell proliferation	2	166.0×	0.006	ABL1, NOTCH1
positive regulation of release of sequestered calcium ion into cytosol	2	141.6×	0.006	ABL1, BAX
germ cell development	2	130.1×	0.006	MTOR, BAX
homeostasis of number of cells within a tissue	2	126.7×	0.006	NOTCH1, BAX
oligodendrocyte differentiation	2	120.4×	0.006	MTOR, NOTCH1
T cell homeostatic proliferation	1	2407.4×	0.007	BAX
coronary sinus valve morphogenesis	1	2407.4×	0.007	NOTCH1
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	2407.4×	0.007	NOTCH1
obsolete GMP catabolic process to guanine	1	2407.4×	0.007	NT5C2
foregut morphogenesis	1	2407.4×	0.007	NOTCH1
release of matrix enzymes from mitochondria	1	2407.4×	0.007	BAX
positive regulation of developmental pigmentation	1	2407.4×	0.007	BAX
regulation of epithelial cell proliferation involved in prostate gland development	1	2407.4×	0.007	NOTCH1
venous endothelial cell differentiation	1	2407.4×	0.007	NOTCH1
positive regulation of SCF-dependent proteasomal ubiquitin-dependent catabolic process	1	2407.4×	0.007	MTOR
protein localization to cytoplasmic microtubule plus-end	1	2407.4×	0.007	ABL1
intrinsic apoptotic signaling pathway in response to DNA damage	2	92.6×	0.007	ABL1, BAX
positive regulation of stress fiber assembly	2	89.2×	0.007	MTOR, ABL1
cellular response to amino acid stimulus	2	87.5×	0.007	DNMT3A, MTOR
negative regulation of BMP signaling pathway	2	83.0×	0.007	ABL1, NOTCH1
positive regulation of neuron apoptotic process	2	77.7×	0.007	ABL1, BAX
apoptotic signaling pathway	2	64.2×	0.007	BAX, BCL10
positive regulation of apoptotic process	3	24.3×	0.007	ABL1, BAX, BCL10
transitional one stage B cell differentiation	1	1203.7×	0.007	ABL1
B cell negative selection	1	1203.7×	0.007	BAX
B cell homeostatic proliferation	1	1203.7×	0.007	BAX

Therapeutics

Drugs indicated or in trials for this disease

9 approved drugs — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Nelarabine	Approved (phase 4)
Calaspargase Pegol	Approved (phase 3)
Cytarabine	Approved (phase 3)
Doxorubicin	Approved (phase 3)
Etoposide	Approved (phase 3)
Ifosfamide	Approved (phase 3)
Methotrexate	Approved (phase 3)
Pegaspargase	Approved (phase 3)
Thioguanine	Approved (phase 3)

19 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Dexamethasone	Phase 3
Filgrastim	Phase 3
Hydrocortisone	Phase 3
Methylprednisolone	Phase 3
Prednisolone	Phase 3
Prednisone	Phase 3
Alemtuzumab	Phase 2
Asparaginase	Phase 2
Blinatumomab	Phase 2
Bortezomib	Phase 2
Daratumumab	Phase 2
Denileukin Diftitox	Phase 2
Etoposide Phosphate	Phase 2
Hyaluronidase	Phase 2
Lenalidomide	Phase 2
Rituximab	Phase 2
Tucidinostat	Phase 2
Venetoclax	Phase 2
Vincristine	Phase 2

Drug target analysis

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

Druggability breadth: 6 of 7 evidence-associated genes (86%) 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
MTOR	SALMETEROL XINAFOATE
ABL1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MTOR	164	4
ABL1	122	4
NOTCH1	1	2
BAX	1	1
DNMT3A	0	0
NT5C2	0	0
BCL10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SALMETEROL XINAFOATE	4	MTOR
IMIPRAMINE	4	MTOR
AMOXAPINE	4	MTOR
IDARUBICIN	4	MTOR
TETRABENAZINE	4	MTOR
TEMSIROLIMUS	4	MTOR
MIFEPRISTONE	4	MTOR
ZIPRASIDONE HYDROCHLORIDE	4	MTOR
PIMOZIDE	4	MTOR
NAFTOPIDIL	4	MTOR
NICLOSAMIDE	4	MTOR
FELODIPINE	4	MTOR
NICARDIPINE	4	MTOR
AZACITIDINE	4	MTOR
TRIFLUPERIDOL	4	MTOR
CYCLOSPORINE	4	MTOR
CLEMASTINE	4	MTOR
TERFENADINE	4	MTOR
FLUOROURACIL	4	MTOR
PANCURONIUM	4	MTOR
EVEROLIMUS	4	MTOR
NIFEDIPINE	4	MTOR
PRAZOSIN	4	MTOR
MAPROTILINE	4	MTOR
DOMPERIDONE	4	MTOR
ALPELISIB	4	MTOR
TACROLIMUS ANHYDROUS	4	MTOR
EBASTINE	4	MTOR
MASOPROCOL	4	MTOR
COPANLISIB	4	MTOR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
MTOR	1,375	Binding:1335, Functional:37, ADMET:2, Toxicity:1
DNMT3A	120	Binding:118, ADMET:1, Functional:1
BAX	49	Binding:47, Functional:2
NOTCH1	23	Binding:19, ADMET:4
NT5C2	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DNMT3A	2.1.1.37	DNA (cytosine-5-)-methyltransferase
NT5C2	3.1.3.5	5’-nucleotidase
ABL1	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
DNMT3A	120
MTOR	1,375
ABL1	3,282

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
SALMETEROL XINAFOATE	4	MTOR
IMIPRAMINE	4	MTOR
AMOXAPINE	4	MTOR
IDARUBICIN	4	MTOR
TETRABENAZINE	4	MTOR
TEMSIROLIMUS	4	MTOR
MIFEPRISTONE	4	MTOR
ZIPRASIDONE HYDROCHLORIDE	4	MTOR
PIMOZIDE	4	MTOR
NAFTOPIDIL	4	MTOR
NICLOSAMIDE	4	MTOR
FELODIPINE	4	MTOR
NICARDIPINE	4	MTOR
AZACITIDINE	4	MTOR
TRIFLUPERIDOL	4	MTOR
CYCLOSPORINE	4	MTOR
CLEMASTINE	4	MTOR
TERFENADINE	4	MTOR
FLUOROURACIL	4	MTOR
PANCURONIUM	4	MTOR
EVEROLIMUS	4	MTOR
NIFEDIPINE	4	MTOR
PRAZOSIN	4	MTOR
MAPROTILINE	4	MTOR
DOMPERIDONE	4	MTOR
ALPELISIB	4	MTOR
TACROLIMUS ANHYDROUS	4	MTOR
EBASTINE	4	MTOR
MASOPROCOL	4	MTOR
COPANLISIB	4	MTOR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	MTOR, ABL1
B	Phased (≥1) drug, not yet approved	2	NOTCH1, BAX
C	Druggable family + PDB, no drug	2	DNMT3A, NT5C2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BCL10

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNMT3A	120	—
NT5C2	7	—
BCL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 82.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	29
PHASE2	18
PHASE1/PHASE2	17
Not specified	8
PHASE3	4
EARLY_PHASE1	4
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03007147	PHASE3	ACTIVE_NOT_RECRUITING	Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
NCT05602194	PHASE3	ACTIVE_NOT_RECRUITING	Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
NCT06381817	PHASE3	RECRUITING	Haplo-cord HCT vs. Haplo-HCT for T-ALL Patients
NCT06855810	PHASE2/PHASE3	RECRUITING	Newly-diagnosed Pediatric T-cell ALL Protocol
NCT07072585	PHASE2/PHASE3	NOT_YET_RECRUITING	Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL)
NCT00408005	PHASE3	COMPLETED	Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
NCT00501826	PHASE2	RECRUITING	Combination Chemotherapy and Nelarabine in Treating Patients With T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
NCT03504644	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Venetoclax and Vincristine in Treating Patients With Relapsed or Refractory T-cell or B-cell Acute Lymphoblastic Leukemia
NCT04128501	PHASE2	ACTIVE_NOT_RECRUITING	Venetoclax and Azacitidine for the Treatment of Acute Myeloid Leukemia in the Post-Transplant Setting
NCT04315324	PHASE1/PHASE2	RECRUITING	Study to Test OBI-3424 in Patients With T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LBL)
NCT05289687	PHASE2	RECRUITING	Daratumumab for Chemotherapy-Refractory Minimal Residual Disease in T Cell ALL
NCT05376111	PHASE2	RECRUITING	Study of Venetoclax Combined With Azacitidine Regimen in Newly Diagnosed T-ALL Patients
NCT06064903	PHASE1/PHASE2	RECRUITING	CD7-CAR-T Cells in Pediatric Relapsed/Refractory CD7+ T-ALL/LL
NCT06316427	PHASE1/PHASE2	RECRUITING	Autologous and Donor-derived CD7 CAR-T Therapy in Refractory or Relapsed T-cell Malignancies
NCT06316856	PHASE1/PHASE2	RECRUITING	CD5 Chimeric Antigen Receptor (CAR) T Cells in Subjects With Relapsed or Refractory T-cell Malignancies
NCT06390319	PHASE2	RECRUITING	Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL)
NCT06420076	PHASE1/PHASE2	RECRUITING	Sequential CAR-T Cells Therapy for CD5/CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD5/CD7-Specific CAR-T Cells
NCT06514794	PHASE2	RECRUITING	A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (T-RRex)
NCT06561074	PHASE2	RECRUITING	A Phase 2 Study to Evaluate Efficacy of Calaspargase Pegol-mknl and Decitabine Combined With Venetoclax in Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) and T- Cell Lymphoblastic Lymphoma (T-LLy)
NCT06648889	PHASE2	RECRUITING	Isatuximab in Adult Patients With Cytologic or Molecular Relapsed/Refractory CD38 Positive T-cell Acute Lymphoblastic Leukemia
NCT06686108	PHASE2	RECRUITING	Demethylating Agents Combined With Venetoclax for High-risk T-cell Lymphoblastic Lymphoma/Leukemia Post-Transplant Relapse Prevention
NCT06738368	PHASE2	RECRUITING	Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia
NCT06911710	PHASE1/PHASE2	RECRUITING	The Application of CAR-T Cell Therapy in Relapsed and Refractory Malignant Hematologic Tumors
NCT07012447	PHASE2	RECRUITING	Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations
NCT07021677	PHASE2	RECRUITING	Use of a New Medicine Daratumumab to Treat Left-over Cancer in a Blood Cancer Called T Acute Lymphoblastic Leukemia
NCT07070323	PHASE1/PHASE2	RECRUITING	A Multicenter, Open-Label, Non-Randomized, Single-Arm Clinical Study of Nanobody CD5-CAR T Cell Therapy for Refractory/Relapsed T Lymphocyte Malignancies
NCT02484430	PHASE2	COMPLETED	Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia
NCT02518113	PHASE1/PHASE2	COMPLETED	A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
NCT02538926	PHASE2	WITHDRAWN	Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
NCT02763384	PHASE2	TERMINATED	BL-8040 and Nelarabine for Relapsed or Refractory T-Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma
NCT02767934	PHASE2	TERMINATED	Pembrolizumab in Treating Minimal Residual Disease in Patients With Acute Lymphoblastic Leukemia
NCT03422679	PHASE1/PHASE2	TERMINATED	Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies
NCT03613428	PHASE1/PHASE2	UNKNOWN	Ruxolitinib Plus LVP in Patients With R/R ETP-ALL
NCT03808610	PHASE1/PHASE2	TERMINATED	Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia
NCT04033302	PHASE1/PHASE2	UNKNOWN	Multi-CAR T Cell Therapy Targeting CD7-positive Malignancies
NCT05032183	PHASE1/PHASE2	TERMINATED	Tagraxofusp and Low-Intensity Chemotherapy for the Treatment of CD123 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
NCT05320380	PHASE1/PHASE2	WITHDRAWN	A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat
NCT05598593	PHASE2	UNKNOWN	Modified TBF Regimen as Conditioning Regimen Prior to Allo-HSCT for T-ALL/LBL
NCT05909527	PHASE1/PHASE2	WITHDRAWN	A Clinical Study of CAR-T Treating Relapsed or Refractory T Cell Lymphoblastic Acute Leukemia/ Lymphoma
NCT06210750	PHASE2	WITHDRAWN	Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MERCAPTOPURINE ANHYDROUS	4	13
NELARABINE	4	7
CALASPARGASE PEGOL	4	6
PEGASPARGASE	4	6
THIOGUANINE	4	5
DEXRAZOXANE	4	3
IMATINIB	4	3
ASPARAGINASE	4	2
DASATINIB ANHYDROUS	4	2
DAUNORUBICIN HYDROCHLORIDE	4	2
VENETOCLAX	4	2
ASPARAGINASE ERWINIA CHRYSANTHEMI	4	1
DARATUMUMAB	4	1
HYDROCORTISONE SODIUM SUCCINATE	4	1
IFOSFAMIDE	4	1
ISATUXIMAB	4	1
LEUCOVORIN	4	1
LEVOCARNITINE	4	1
LEVOLEUCOVORIN	4	1
OMACETAXINE MEPESUCCINATE	4	1
PEMBROLIZUMAB	4	1
RANITIDINE	4	1
TAGRAXOFUSP	4	1
CARNITINE	3	1
MOTIXAFORTIDE	3	1
NAVITOCLAX	3	1
CRENIGACESTAT	2	1
FLOTETUZUMAB	2	1
LIMANTRAFIN	2	1
SAPANISERTIB	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 18 predictive associations from 19 curated evidence items; also 2 diagnostic, 1 prognostic, 1 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
NOTCH1 Mutation	Prednisone	Sensitivity/Response	CIViC C	EID2692 +1
NOTCH1 F1592C	Prednisone	Sensitivity/Response	CIViC C	EID2852
NOTCH1 F1592S	Prednisone	Sensitivity/Response	CIViC C	EID2821
NOTCH1 L1574P	Prednisone	Sensitivity/Response	CIViC C	EID2691
NOTCH1 L1574Q	Prednisone	Sensitivity/Response	CIViC C	EID2826
NOTCH1 L1585R	Prednisone	Sensitivity/Response	CIViC C	EID2823
NOTCH1 L1600P	Prednisone	Sensitivity/Response	CIViC C	EID2690
NOTCH1 L1600Q	Prednisone	Sensitivity/Response	CIViC C	EID2822
NOTCH1 V1577A	Prednisone	Sensitivity/Response	CIViC C	EID2824
NOTCH1 V1577E	Prednisone	Sensitivity/Response	CIViC C	EID2825
JAK3 M511I	Tofacitinib	Sensitivity/Response	CIViC D	EID2977
MTOR C1483Y	Sirolimus	Sensitivity/Response	CIViC D	EID1320
NT5C2 D407A	Thioguanine + Mercaptopurine	Resistance	CIViC D	EID632
NT5C2 D407A	Nelarabine + Arabinosylguanine	Resistance	CIViC D	EID635
NT5C2 K359Q	Mercaptopurine + Thioguanine	Resistance	CIViC D	EID631
NT5C2 K359Q	Arabinosylguanine + Nelarabine	Resistance	CIViC D	EID636
NT5C2 R367Q	Mercaptopurine + Thioguanine	Resistance	CIViC D	EID630
NT5C2 R367Q	Nelarabine + Arabinosylguanine	Resistance	CIViC D	EID633