Acute leukemia

Summary

Acute leukemia (MONDO:0010643) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 213 clinical trials. Molecularly, KMT2A Translocation confers sensitivity to Revumenib in Acute Leukemia (CIViC Level A); 9 further subtype–drug associations are mapped below. Top therapeutic interventions include revumenib, daunorubicin, and palifermin.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 213
• Precision-medicine evidence (CIViC): 10 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acute leukemia
Mondo ID	MONDO:0010643
EFO	EFO:1000068
MeSH	C564112
DOID	DOID:12603
NCIT	C9300
SNOMED CT	91855006
UMLS	C0085669
MedGen	43225
GARD	0024743
Is cancer (heuristic)	yes

Also known as: acute leukaemia (disease) · acute leukemia · acute leukemia (disease) · stem cell leukaemia · stem cell leukaemia (disease) · stem cell leukemia (disease)

Data availability: 1 HPO phenotype.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › 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 › leukemia › acute leukemia

Related subtypes (11): chronic leukemia, chronic erythremia, testicular leukemia, central nervous system leukemia, aleukemic leukemia, splenic manifestation of leukemia, childhood leukemia, monocytic leukemia, myeloid leukemia, lymphoid leukemia, mast cell leukemia

Subtypes (4): subacute leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, leukemia, acute, X-linked

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

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
nipple	1
pylorus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRAS	14,509

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 71. 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
Signaling by RAS GAP mutants	1	3806.7×	0.003	KRAS
Signaling by RAS GTPase mutants	1	3806.7×	0.003	KRAS
Activation of RAS in B cells	1	2284.0×	0.003	KRAS
RAS signaling downstream of NF1 loss-of-function variants	1	1631.4×	0.003	KRAS
Estrogen-stimulated signaling through PRKCZ	1	1631.4×	0.003	KRAS
SOS-mediated signalling	1	1427.5×	0.003	KRAS
Activated NTRK3 signals through RAS	1	1268.9×	0.003	KRAS
EGFR Transactivation by Gastrin	1	1142.0×	0.003	KRAS
SHC-related events triggered by IGF1R	1	1142.0×	0.003	KRAS
RUNX3 regulates p14-ARF	1	1142.0×	0.003	KRAS
Activated NTRK2 signals through RAS	1	1142.0×	0.003	KRAS
MET activates RAS signaling	1	1038.2×	0.003	KRAS
Signaling by FGFR4 in disease	1	951.7×	0.003	KRAS
Activated NTRK2 signals through FRS2 and FRS3	1	951.7×	0.003	KRAS
Constitutive Signaling by Overexpressed ERBB2	1	951.7×	0.003	KRAS
p38MAPK events	1	878.5×	0.003	KRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	878.5×	0.003	KRAS
Signaling by PDGFRA extracellular domain mutants	1	878.5×	0.003	KRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	815.7×	0.003	KRAS
GRB2 events in EGFR signaling	1	761.3×	0.003	KRAS
Erythropoietin activates RAS	1	761.3×	0.003	KRAS
Signaling by FLT3 ITD and TKD mutants	1	761.3×	0.003	KRAS
SHC1 events in ERBB4 signaling	1	713.8×	0.003	KRAS
SHC1 events in EGFR signaling	1	713.8×	0.003	KRAS
Constitutive Signaling by EGFRvIII	1	713.8×	0.003	KRAS
Signalling to RAS	1	671.8×	0.003	KRAS
Insulin receptor signalling cascade	1	671.8×	0.003	KRAS
Signaling by ERBB2 ECD mutants	1	671.8×	0.003	KRAS
GRB2 events in ERBB2 signaling	1	634.4×	0.003	KRAS
Tie2 Signaling	1	601.0×	0.003	KRAS

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
response to mineralocorticoid	1	16852.0×	0.002	KRAS
forebrain astrocyte development	1	5617.3×	0.002	KRAS
response to isolation stress	1	4213.0×	0.002	KRAS
response to gravity	1	2808.7×	0.003	KRAS
type I pneumocyte differentiation	1	1532.0×	0.003	KRAS
myoblast proliferation	1	1404.3×	0.003	KRAS
positive regulation of cellular senescence	1	1296.3×	0.003	KRAS
negative regulation of epithelial cell differentiation	1	1203.7×	0.003	KRAS
regulation of synaptic transmission, GABAergic	1	1053.2×	0.003	KRAS
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.003	KRAS
striated muscle cell differentiation	1	991.3×	0.003	KRAS
glial cell proliferation	1	887.0×	0.003	KRAS
epithelial tube branching involved in lung morphogenesis	1	842.6×	0.003	KRAS
positive regulation of glial cell proliferation	1	702.2×	0.003	KRAS
positive regulation of Rac protein signal transduction	1	648.1×	0.003	KRAS
cardiac muscle cell proliferation	1	581.1×	0.003	KRAS
Rac protein signal transduction	1	561.7×	0.003	KRAS
homeostasis of number of cells within a tissue	1	443.5×	0.004	KRAS
skeletal muscle cell differentiation	1	343.9×	0.005	KRAS
response to glucocorticoid	1	324.1×	0.005	KRAS
visual learning	1	306.4×	0.005	KRAS
liver development	1	221.7×	0.006	KRAS
female pregnancy	1	210.7×	0.006	KRAS
Ras protein signal transduction	1	205.5×	0.006	KRAS
neuron apoptotic process	1	185.2×	0.007	KRAS
MAPK cascade	1	153.2×	0.008	KRAS
cytokine-mediated signaling pathway	1	130.6×	0.009	KRAS
negative regulation of neuron apoptotic process	1	110.9×	0.010	KRAS
gene expression	1	79.9×	0.013	KRAS
actin cytoskeleton organization	1	79.1×	0.013	KRAS

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KRAS	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	KRAS
DABRAFENIB	4	KRAS
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS
OPNURASIB	3	KRAS
DIVARASIB	2	KRAS
GLECIRASIB	2	KRAS
BMS-214662	1	KRAS
LY-3009120	1	KRAS
MRTX-1133	1	KRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KRAS	861	Binding:829, Functional:32

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
KRAS	861

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

11 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)
VEMURAFENIB	4	KRAS
DABRAFENIB	4	KRAS
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS
OPNURASIB	3	KRAS
DIVARASIB	2	KRAS
GLECIRASIB	2	KRAS
BMS-214662	1	KRAS
LY-3009120	1	KRAS
MRTX-1133	1	KRAS

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	KRAS
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 213.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	101
PHASE2	43
PHASE1/PHASE2	26
PHASE1	26
PHASE3	8
PHASE2/PHASE3	5
PHASE4	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05071482	PHASE4	TERMINATED	Flumatinib Versus Imatinib Combined With Chemotherapy for de Novo Ph+ ALL
NCT05634915	PHASE4	UNKNOWN	Clinical Study of rATG Individualized Administration in Haploidentical Hematopoietic Stem Cell Transplantation
NCT05316701	PHASE3	ACTIVE_NOT_RECRUITING	Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies
NCT05328258	PHASE3	RECRUITING	Use of GnRHa During Chemotherapy for Fertility Protection
NCT07157514	PHASE2/PHASE3	NOT_YET_RECRUITING	Radioimmunotherapy Conditioning With 131I- Apamistamab for Allogeneic Transplant in Relapse/Refractory AML
NCT00914628	PHASE3	TERMINATED	Efficacy Study on the Strategy of HSV-Tk Engineering Donor Lymphocytes to Treat Patients With High Risk Acute Leukemia
NCT01020175	PHASE3	COMPLETED	Peripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
NCT01385891	PHASE2/PHASE3	COMPLETED	Clove In The Treatment Of Relapsed Or Resistant Acute Leukemia In Children
NCT01800643	PHASE2/PHASE3	UNKNOWN	Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
NCT02345850	PHASE3	COMPLETED	Calcineurin Inhibitor-Free Interventions BMT CTN 1301 for Prevention of Graft-versus-Host Disease (BMT CTN 1301)
NCT02730299	PHASE3	COMPLETED	Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard UCB in Patients With Leukemia, Lymphoma, and MDS
NCT03595800	PHASE3	COMPLETED	Extension of a Study of Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor or From an Unrelated Donor to Younger Patients Eligible for Reduced-intensity Conditioning Regimen
NCT03959241	PHASE3	COMPLETED	TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)
NCT04674345	PHASE2/PHASE3	UNKNOWN	Sorafenib Maintenance for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3 Negative Acute Leukemia
NCT05739630	PHASE2/PHASE3	UNKNOWN	M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia
NCT03314974	PHASE2	RECRUITING	Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
NCT03779854	PHASE2	RECRUITING	Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant
NCT03970096	PHASE2	RECRUITING	Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia or Myelodysplastic Syndrome (MDS)
NCT04099966	PHASE2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT04187105	PHASE2	RECRUITING	BMT-06: Study of Intensity Modulated Total Marrow Irradiation (IM-TMI)
NCT04195633	PHASE2	RECRUITING	Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
NCT04202835	PHASE2	ACTIVE_NOT_RECRUITING	ATG Plus PTCy vs ATG for CGVHD Prophylaxis
NCT04451200	PHASE2	NOT_YET_RECRUITING	Sequential and Personalized PK-guided Busulfan Administration in the Frame of the Conditiong Regimen for Allo-HSCT in Patients With Malignant Hemopathies Ineligible for the Standard Myeloablative Conditioning
NCT04811560	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of Bleximenib in Participants With Acute Leukemia (cAMeLot-1)
NCT04904588	PHASE2	ACTIVE_NOT_RECRUITING	HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
NCT05521204	PHASE2	RECRUITING	Olverembatinib for FGFR1-rearranged Neoplasms
NCT05589896	PHASE1/PHASE2	RECRUITING	A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
NCT05735717	PHASE2	RECRUITING	MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC Transplantation for Heme Malignancies
NCT06001385	PHASE2	ACTIVE_NOT_RECRUITING	HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis
NCT06052813	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of BN104 in the Treatment of Acute Leukemia
NCT06058572	PHASE2	RECRUITING	Effect of Rifaximin on Gut Bacterial Flora Post Stem Cell Transplant in Patients With Acute Leukemia
NCT06207123	PHASE1/PHASE2	RECRUITING	A Study to Investigate LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL)
NCT06265584	PHASE2	RECRUITING	Trial of 2 Step ATG for Prevention of Acute GVHD Post Allogeneic Stem Cell Transplant
NCT06315309	PHASE2	RECRUITING	Trial of 2 Step ATG for Acute GVHD Prevention Post Myeloablative Allogeneic Stem Cell Transplant
NCT06356922	PHASE1/PHASE2	RECRUITING	Study Assessing RLT Using [177Lu]Lu-PentixaTher for Relapsed/Refractory CXCR4+ Acute Leukemia.
NCT06585345	PHASE1/PHASE2	RECRUITING	Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell in Patients With Relapsed/Refractory Acute Leukemia
NCT06859424	PHASE2	RECRUITING	A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
NCT06984536	PHASE2	RECRUITING	Reduced ATG Plus Mini PTCy for GVHD Prophylaxis in Haplo-SCT
NCT07101497	PHASE2	RECRUITING	Phase 2 Trial of BN104 as Post-HSCT Maintenance in Acute Leukemia
NCT07356154	PHASE1/PHASE2	RECRUITING	A Study of Revumenib and Mezigdomide in People With Leukemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
REVUMENIB	4	3
DAUNORUBICIN	4	2
PALIFERMIN	4	2
TOCILIZUMAB	4	2
TREOSULFAN	4	2
CLOFARABINE	4	1
DIPHENHYDRAMINE	4	1
ELTROMBOPAG	4	1
ETOPOSIDE PHOSPHATE	4	1
GILTERITINIB	4	1
IMATINIB	4	1
IXAZOMIB CITRATE	4	1
LURBINECTEDIN	4	1
LUSPATERCEPT	4	1
MARAVIROC	4	1
MELPHALAN HYDROCHLORIDE	4	1
MICAFUNGIN	4	1
MITOXANTRONE	4	1
MYCOPHENOLATE SODIUM	4	1
PONATINIB	4	1
PROTEIN C CONCENTRATE (HUMAN)	4	1
PROTEIN S HUMAN	4	1
SORAFENIB	4	1
TRIPTORELIN PAMOATE	4	1
ANTITHROMBIN III HUMAN	3	1
FLUMATINIB	3	1
MEZIGDOMIDE	3	1
NALOTIMAGENE CARMALEUCEL	3	1
OLVEREMBATINIB	3	1
BLEXIMENIB	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 10 predictive associations from 10 curated evidence items; also 1 oncogenic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
KMT2A Translocation	Revumenib	Sensitivity/Response	CIViC A	EID12214
MEN1 G326D	Revumenib + VTP-50469	Resistance	CIViC B	EID12737
MEN1 G326R	Revumenib + VTP-50469	Resistance	CIViC B	EID12734
MEN1 M322I	Revumenib + VTP-50469	Resistance	CIViC B	EID12730
MEN1 Mutation	Revumenib	Resistance	CIViC B	EID12717
MEN1 T344M	Revumenib + VTP-50469	Resistance	CIViC B	EID12733
MEN1 S155T	Revumenib + VTP-50469	Resistance	CIViC C	EID12741
KMT2A Rearrangement	VTP50469 + Menin Inhibitor	Sensitivity/Response	CIViC D	EID7819
MEN1 M322V	VTP-50469 + Revumenib	Resistance	CIViC D	EID12728
MEN1 S155C	VTP-50469	Resistance	CIViC D	EID12742