Acute monocytic leukemia

Summary

Acute monocytic leukemia (MONDO:0007896) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 11 clinical trials. Top therapeutic interventions include ascorbic acid, cladribine, and hyaluronidase (human recombinant).

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 20
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.13	Europe	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0004845	Acute monocytic leukemia	Obligate (100%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002875	Exertional dyspnea	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0031020	Bone marrow hypercellularity	Frequent (30-79%)
HP:0100827	Lymphocytosis	Frequent (30-79%)
HP:0001482	Subcutaneous nodule	Occasional (5-29%)
HP:0001730	Progressive hearing impairment	Occasional (5-29%)
HP:0001785	Ankle swelling	Occasional (5-29%)
HP:0001824	Weight loss	Occasional (5-29%)
HP:0001931	Hypochromic anemia	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002039	Anorexia	Occasional (5-29%)
HP:0011787	Central hypothyroidism	Occasional (5-29%)
HP:0012145	Abnormality of multiple cell lineages in the bone marrow	Occasional (5-29%)
HP:0025289	Cervical lymphadenopathy	Occasional (5-29%)
HP:0025435	Increased circulating lactate dehydrogenase concentration	Occasional (5-29%)
HP:0100520	Oliguria	Occasional (5-29%)
HP:0100539	Periorbital edema	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acute monocytic leukemia
Mondo ID	MONDO:0007896
EFO	EFO:0000221
MeSH	D007948
OMIM	151380
Orphanet	514
DOID	DOID:8864
ICD-10-CM	C93.0
ICD-11	517546180
NCIT	C4861
SNOMED CT	413441006
UMLS	C0023465
MedGen	7319
GARD	0000525
MedDRA	10000871, 10059439
Is cancer (heuristic)	yes

Also known as: acute monoblastic leukaemia · acute monoblastic leukaemia and acute monocytic leukaemia · acute monoblastic leukemia · acute monoblastic/monocytic leukaemia · acute monoblastic/monocytic leukemia · acute monocytic leukaemia (FAB M5B) · acute monocytic leukaemia (FAB M5b) · acute monocytic leukemia · acute monocytic leukemia (FAB M5B) · acute monocytic leukemia (FAB M5b) · acute monocytic leukemia, morphology (morphologic abnormality) · acute myeloblastic leukaemia type 5 · acute myeloblastic leukemia type 5 · AML M5 · AML-M5 · leukemia, monocytic, malignant · monocytic leukaemia · monocytic leukemia · monocytic leukemia, acute

Data availability: 1 ClinVar variant · 554 cell lines.

Disease family

An umbrella term covering 3 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 › monocytic leukemia › acute monocytic leukemia

Related subtypes (1): chronic monocytic leukemia

Subtypes (3): adult acute monocytic leukemia, aleukemic monocytic leukemia cutis, subacute monocytic 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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
229977	NM_001042492.3(NF1):c.2747A>G (p.Asn916Ser)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
NF1	LoF	ACC,ALL,AML,ANGS,BLCA,BRCA,CCRCC,CHOL,CLLSLL,COADREAD,GB,GBM,GIST,HCC,HNSC,LGGNOS,LMS,LUAD,LUNG,LUSC,MEL,NBL,NSCLC,OVT,PAST,PGNG,PLMESO,RMS,SKCM,SOFT_TISSUE,STAD,THYM,UCS	CIViC #3867

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma

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
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot

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
adrenal tissue	1
calcaneal tendon	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NF1	5,540

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NF1	P21359	26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
RAS signaling downstream of NF1 loss-of-function variants	1	1631.4×	0.006	NF1
Oncogenic MAPK signaling	1	248.3×	0.015	NF1
Regulation of RAS by GAPs	1	193.6×	0.015	NF1
MAPK1/MAPK3 signaling	1	131.3×	0.017	NF1
MAPK family signaling cascades	1	102.9×	0.017	NF1
RAF/MAP kinase cascade	1	61.1×	0.023	NF1
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.023	NF1
Disease	1	13.1×	0.086	NF1
Signal Transduction	1	10.2×	0.098	NF1

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
positive regulation of mast cell apoptotic process	1	16852.0×	0.002	NF1
regulation of glial cell differentiation	1	16852.0×	0.002	NF1
observational learning	1	16852.0×	0.002	NF1
gamma-aminobutyric acid secretion, neurotransmission	1	8426.0×	0.002	NF1
Schwann cell proliferation	1	5617.3×	0.002	NF1
forebrain astrocyte development	1	5617.3×	0.002	NF1
Schwann cell migration	1	5617.3×	0.002	NF1
glutamate secretion, neurotransmission	1	5617.3×	0.002	NF1
negative regulation of mast cell proliferation	1	5617.3×	0.002	NF1
negative regulation of Schwann cell migration	1	5617.3×	0.002	NF1
vascular associated smooth muscle cell migration	1	5617.3×	0.002	NF1
mast cell apoptotic process	1	4213.0×	0.002	NF1
negative regulation of Rac protein signal transduction	1	4213.0×	0.002	NF1
myeloid leukocyte migration	1	4213.0×	0.002	NF1
mast cell proliferation	1	3370.4×	0.002	NF1
amygdala development	1	2808.7×	0.002	NF1
regulation of blood vessel endothelial cell migration	1	2808.7×	0.002	NF1
vascular associated smooth muscle cell proliferation	1	2808.7×	0.002	NF1
negative regulation of Schwann cell proliferation	1	2407.4×	0.002	NF1
negative regulation of neurotransmitter secretion	1	2407.4×	0.002	NF1
hair follicle maturation	1	2106.5×	0.002	NF1
negative regulation of leukocyte migration	1	1685.2×	0.002	NF1
negative regulation of vascular associated smooth muscle cell migration	1	1685.2×	0.002	NF1
regulation of bone resorption	1	1532.0×	0.002	NF1
negative regulation of astrocyte differentiation	1	1532.0×	0.002	NF1
regulation of long-term synaptic potentiation	1	1532.0×	0.002	NF1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	1532.0×	0.002	NF1
forebrain morphogenesis	1	1404.3×	0.002	NF1
regulation of cell-matrix adhesion	1	1296.3×	0.003	NF1
negative regulation of neuroblast proliferation	1	1203.7×	0.003	NF1

Therapeutics

Drugs indicated or in trials for this disease

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

Drug	Status
Asparaginase	Approved (phase 3)
Busulfan	Approved (phase 3)
Cytarabine	Approved (phase 3)
Etoposide	Approved (phase 3)
Fludarabine Phosphate	Approved (phase 3)
Idarubicin	Approved (phase 3)
Methotrexate	Approved (phase 3)
Thioguanine	Approved (phase 3)

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

Drug	Highest phase
Aldesleukin	Phase 3
Dexamethasone	Phase 3
Filgrastim	Phase 3
Hydrocortisone	Phase 3
Valspodar	Phase 3
Azacitidine	Phase 2
Tucidinostat	Phase 2
Venetoclax	Phase 2

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
NF1	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	NF1

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)
NF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	5
PHASE1	3
PHASE1/PHASE2	1
EARLY_PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05566054	PHASE2	RECRUITING	Venetoclax and Azacitidine Combined With Chidamide (VAC) for the Treatment of Newly Diagnosed Acute Monocytic Leukemia
NCT06504459	PHASE2	RECRUITING	Venetoclax in Combination With Cladribine and Cytarabine Alternating With Azacitidine Plus Venetoclax for the Treatment of Newly Diagnosed Monocytic AML and Active Signaling Mutated AML
NCT07292272	PHASE2	RECRUITING	Halt Aging in Survivors of Blood Cancers
NCT07512700	PHASE2	RECRUITING	Venetoclax Combined With CACAG Regimen Versus 3+7 Regimen in the Treatment of Acute Monocytic Leukemia
NCT03613727	PHASE2	COMPLETED	Therapeutic Use of Intravenous Vitamin C in Allogeneic Stem Cell Transplant Recipients
NCT05282459	PHASE1/PHASE2	COMPLETED	Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation
NCT06429449	PHASE1	RECRUITING	Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
NCT06950034	PHASE1	RECRUITING	A Phase 1 Study of STX-0712 in Patients With Advanced Hematological Malignancies (CMML and AML)
NCT04714372	PHASE1	COMPLETED	FT538 in Combination With Daratumumab in AML Acute Myeloid Leukemia
NCT04803929	EARLY_PHASE1	UNKNOWN	Clinical Study of Anti-ILT3 CAR-T Therapy for R/R AML(M4/M5)
NCT05871008	Not specified	ACTIVE_NOT_RECRUITING	Integrated Actionable Aging Assessment for Cancer Patients Pilot

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASCORBIC ACID	4	1
CLADRIBINE	4	1
HYALURONIDASE (HUMAN RECOMBINANT)	4	1
TUCIDINOSTAT	3	1
CHEMBL4087968	0	1
CHEMBL4776881	0	1