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Atlas / Disease / acute myeloid leukemia with mutated NPM1

acute myeloid leukemia with mutated NPM1

disease
On this page

Also known as acute myeloid leukaemia with cytoplasmic nucleophosminacute myeloid leukemia with cytoplasmic nucleophosminacute myeloid leukemia, NPM1 gene mutationAML with mutated NPM1AML, Mutation of the Nucleophosmin GeneAML, NPM1 gene mutationAML, NPM1 MutationAML, Nucleophosmin Gene MutationNPMc+ AML

Summary

acute myeloid leukemia with mutated NPM1 (MONDO:0044923) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers) and 4 clinical trials. Top therapeutic interventions include azacitidine, gilteritinib, and quizartinib.

At a glance

  • Classification: Cancer
  • Cohort genes: 2
  • Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameacute myeloid leukemia with mutated NPM1
Mondo IDMONDO:0044923
DOIDDOID:0081089
NCITC82431
UMLSC2826177
MedGen414842
GARD0025924
Is cancer (heuristic)yes

Also known as: acute myeloid leukaemia with cytoplasmic nucleophosmin · acute myeloid leukemia with cytoplasmic nucleophosmin · acute myeloid leukemia with mutated NPM1 · acute myeloid leukemia, NPM1 gene mutation · AML with mutated NPM1 · AML, Mutation of the Nucleophosmin Gene · AML, NPM1 gene mutation · AML, NPM1 Mutation · AML, Nucleophosmin Gene Mutation · NPMc+ AML

Disease family

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 › leukemia › myeloid leukemia › acute myeloid leukemia › acute myeloid leukemia with mutated NPM1

Related subtypes (77): childhood acute myeloid leukemia, acute monocytic leukemia, acute myeloid leukemia with t(8;21)(q22;q22) translocation, acute myeloid leukemia by FAB classification, inherited acute myeloid leukemia, acute myeloid leukemia with CEBPA somatic mutations, acute myeloid leukemia with t(8;16)(p11;p13) translocation, acute myeloid leukemia with t(6;9)(p23;q34), acute myeloid leukemia with t(9;11)(p22;q23), acute myeloid leukemia with inv3(p21;q26.2) or t(3;3)(p21;q26.2), megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13), acute myeloid leukemia with NPM1 somatic mutations, acute myeloid leukemia with multilineage dysplasia, therapy related acute myeloid leukemia and myelodysplastic syndrome, acute leukemia of ambiguous lineage, acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22), acute myeloid leukemia with 11q23 abnormalities, acute myeloid leukemia with BCR-ABL1, acute myeloid leukemia, inv(16)(p13.1;q22), acute myeloid leukemia, t(16;16)(p13.1;q22), acute myeloid leukemia, t(15;17)(q24;q21), acute myeloid leukemia, t(9;11)(p21.3;q23.3), acute myeloid leukemia, t(10;11)(p12;q23), acute myeloid leukemia, t(10;11)(p11.2;q23), acute myeloid leukemia, t(1;11)(q21;q23), acute myeloid leukemia, t(4;11)(q21;q23), acute myeloid leukemia, t(6;11)(q27;q23), acute myeloid leukemia, t(6;9)(p23;q34.1), acute myeloid leukemia, t(11;19)(q23;p13), acute myeloid leukemia, t(11;19)(q23;p13.1), acute myeloid leukemia, t(11;19)(q23.3;p13.3), acute myeloid leukemia, t(v;11q23.3), acute myeloid leukemia, Monosomy 7, acute myeloid leukemia, Monosomy 5, acute myeloid leukemia, Trisomy 8, acute myeloid leukemia, der12p, acute myeloid leukemia, t(2;12), acute myeloid leukemia, t(11;17), acute myeloid leukemia, t(8;16), acute myeloid leukemia, t(1;22), acute myeloid leukemia, t(5;11)(q35;p15), acute myeloid leukemia, t(7;12)(q36;p13), acute myeloid leukemia, t(9;22)(q34.1;q11.2), acute myeloid leukemia, inv(3)(q21.3;q26.2), acute myeloid leukemia, t(3;3)(q21.3;q26.2), acute myeloid leukemia, t(3;12)(q23;p12.3), acute myeloid leukemia, del(5q31-q32), acute myeloid leukemia, del(13q14-q21), acute myeloid leukemia, loss of chromosome 17p, acute myeloid leukemia, MLL gene rearrangement, acute myeloid leukemia, Non-KMT2A MLLT10 rearrangement positive, acute myeloid leukemia, inv(16)(p13.3;q24.3), acute myeloid leukemia, t(11;15)(p15;q35), acute myeloid leukemia, t(16;21)(q24;q22), acute myeloid leukemia, t(3;5)(q25;q34), acute myeloid leukemia, t(16;21)(p11;q22), acute myeloid leukemia, monoallelic CEBPA gene mutation, acute myeloid leukemia, biallelic CEBPA gene mutation, acute myeloid leukemia, CEBPA gene mutation, acute myeloid leukemia, FLT3 internal tandem duplication, acute myeloid leukemia, FLT3 tyrosine kinase domain point mutation, acute myeloid leukemia, WT1 gene mutation, acute myeloid leukemia, KIT exon 17 mutation, acute myeloid leukemia, KIT exon 8 mutation, acute myeloid leukemia, KIT gene mutation, acute myeloid leukemia, GATA1 gene mutation, acute myeloid leukemia, RUNX1 gene mutation, acute myeloid leukemia, PTPN11 gene mutation, acute myeloid leukemia, NRAS gene mutation, acute myeloid leukemia, KRAS gene mutation, core binding factor acute myeloid leukemia, acute myeloid leukemia, t(8;21)(q22; q22.1), acute myeloid leukemia, t(1;22)(p13;q13), acute myeloid leukemia with CBFA2T3-GLIS2 fusion, acute myeloid leukemia with FUS-ERG fusion, acute myeloid leukemia with MNX1-ETV6 fusion, acute myeloid leukemia with NPM1-MLF1 fusion

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
FLT3ActALL,AMLCIViC #24
NPM1ActHCCCIViC #35

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
FLT3Orphanet:102724Acute myeloid leukemia with t(8;21)(q22;q22) translocation
FLT3Orphanet:585909B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
FLT3Orphanet:589534Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2)
FLT3Orphanet:589595Mixed phenotype acute leukemia with t(v;11q23.3)
FLT3Orphanet:98829Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
FLT3Orphanet:98832Acute myeloid leukemia with minimal differentiation
FLT3Orphanet:98833Acute myeloblastic leukemia without maturation
FLT3Orphanet:98834Acute myeloblastic leukemia with maturation
FLT3Orphanet:99861Precursor T-cell acute lymphoblastic leukemia
NPM1Orphanet:1775Dyskeratosis congenita
NPM1Orphanet:300865Primary cutaneous anaplastic large cell lymphoma
NPM1Orphanet:402026Acute myeloid leukemia with NPM1 somatic mutations
NPM1Orphanet:520Acute promyelocytic leukemia
NPM1Orphanet:98833Acute myeloblastic leukemia without maturation
NPM1Orphanet:98834Acute myeloblastic leukemia with maturation
NPM1Orphanet:98842Lymphomatoid papulosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
FLT3HGNC:3765ENSG00000122025P36888Receptor-type tyrosine-protein kinase FLT3civic_evidence
NPM1HGNC:7910ENSG00000181163P06748Nucleophosmincivic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
FLT3Receptor-type tyrosine-protein kinase FLT3Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.
NPM1NucleophosminInvolved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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.

FamilyGenesFoldFDR
Kinase113.9×0.142
Other/Unknown10.9×0.805

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
FLT3Kinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
NPM1Other/UnknownnoNucleoplasmin, Nucleoplasmin_core_dom, NPM1_C

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
cerebellar cortex1
cerebellar hemisphere1
male germ line stem cell (sensu Vertebrata) in testis1
calcaneal tendon1
left ovary1
ventricular zone1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
FLT3166broadmarkermale germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex
NPM1276ubiquitousmarkercalcaneal tendon, left ovary, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
NPM17,589
FLT33,570

Intra-cohort edges

ABSources
FLT3NPM1string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
FLT3P3688811
NPM1P067488

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
FLT3 mutants bind TKIs15710.0×4e-04FLT3
KW2449-resistant FLT3 mutants15710.0×4e-04FLT3
semaxanib-resistant FLT3 mutants15710.0×4e-04FLT3
crenolanib-resistant FLT3 mutants15710.0×4e-04FLT3
gilteritinib-resistant FLT3 mutants15710.0×4e-04FLT3
lestaurtinib-resistant FLT3 mutants15710.0×4e-04FLT3
midostaurin-resistant FLT3 mutants15710.0×4e-04FLT3
pexidartinib-resistant FLT3 mutants15710.0×4e-04FLT3
ponatinib-resistant FLT3 mutants15710.0×4e-04FLT3
quizartinib-resistant FLT3 mutants15710.0×4e-04FLT3
sorafenib-resistant FLT3 mutants15710.0×4e-04FLT3
sunitinib-resistant FLT3 mutants15710.0×4e-04FLT3
tandutinib-resistant FLT3 mutants15710.0×4e-04FLT3
linifanib-resistant FLT3 mutants15710.0×4e-04FLT3
tamatinib-resistant FLT3 mutants15710.0×4e-04FLT3
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation11142.0×0.002NPM1
STAT5 Activation1815.7×0.002FLT3
FLT3 signaling through SRC family kinases1815.7×0.002FLT3
FLT3 signaling by CBL mutants1815.7×0.002FLT3
STAT5 activation downstream of FLT3 ITD mutants1571.0×0.003FLT3
ALK mutants bind TKIs1475.8×0.004NPM1
Signaling by FLT3 ITD and TKD mutants1380.7×0.004FLT3
Negative regulation of FLT31356.9×0.005FLT3
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain1259.6×0.006NPM1
FLT3 Signaling1173.0×0.008FLT3
Nuclear import of Rev protein1167.9×0.008NPM1
Nuclear events stimulated by ALK signaling in cancer1163.1×0.008NPM1
PI3K Cascade1135.9×0.010FLT3
SUMOylation of transcription cofactors1121.5×0.010NPM1
SARS-CoV-1-host interactions187.8×0.014NPM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of eIF2 alpha phosphorylation by dsRNA18426.0×0.004NPM1
regulation of mRNA stability involved in cellular response to UV18426.0×0.004NPM1
leukocyte homeostasis12808.7×0.004FLT3
positive regulation of cell cycle G2/M phase transition12808.7×0.004NPM1
pro-B cell differentiation12106.5×0.004FLT3
positive regulation of centrosome duplication11685.2×0.004NPM1
negative regulation of centrosome duplication11685.2×0.004NPM1
negative regulation of protein kinase activity by regulation of protein phosphorylation11685.2×0.004NPM1
positive regulation of protein localization to nucleolus11404.3×0.004NPM1
ribosomal large subunit export from nucleus11203.7×0.004NPM1
myeloid progenitor cell differentiation11203.7×0.004FLT3
lymphocyte proliferation11203.7×0.004FLT3
ribosomal small subunit export from nucleus11053.2×0.004NPM1
regulation of DNA damage response, signal transduction by p53 class mediator11053.2×0.004NPM1
common myeloid progenitor cell proliferation1936.2×0.004FLT3
ribosome assembly1936.2×0.004NPM1
positive regulation of cell population proliferation233.6×0.004FLT3, NPM1
regulation of centriole replication1842.6×0.004NPM1
dendritic cell differentiation1526.6×0.006FLT3
negative regulation of mRNA splicing, via spliceosome1383.0×0.007NPM1
regulation of centrosome duplication1366.4×0.007NPM1
positive regulation of tyrosine phosphorylation of STAT protein1366.4×0.007FLT3
positive regulation of MAP kinase activity1324.1×0.008FLT3
cellular response to glucocorticoid stimulus1312.1×0.008FLT3
cell volume homeostasis1300.9×0.008NPM1
cellular response to cytokine stimulus1271.8×0.008FLT3
liver regeneration1255.3×0.009FLT3
macrophage differentiation1234.1×0.009NPM1
ribosomal large subunit biogenesis1221.7×0.009NPM1
peptidyl-tyrosine phosphorylation1210.7×0.009FLT3

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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.

SymbolExample approved molecule
FLT3PONATINIB
NPM1CERITINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
FLT31434
NPM154

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PONATINIB4FLT3
AFATINIB4FLT3
FEDRATINIB4FLT3
TIVOZANIB4FLT3
AXITINIB4FLT3
SORAFENIB4FLT3
NERATINIB4FLT3
INFIGRATINIB PHOSPHATE4FLT3
INFIGRATINIB4FLT3
IBRUTINIB4FLT3
PALBOCICLIB4FLT3
REGORAFENIB4FLT3
ENTRECTINIB4FLT3
PACRITINIB4FLT3
FOSTAMATINIB4FLT3
QUIZARTINIB DIHYDROCHLORIDE4FLT3
CABOZANTINIB4FLT3
CERITINIB4FLT3, NPM1
VANDETANIB4FLT3
NILOTINIB4FLT3
BOSUTINIB4FLT3, NPM1
FILGOTINIB4FLT3
ABEMACICLIB4FLT3
GILTERITINIB4FLT3
BRIGATINIB4FLT3
PEXIDARTINIB4FLT3
PRALSETINIB4FLT3
PAZOPANIB4FLT3
NINTEDANIB4FLT3
SUNITINIB4FLT3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
FLT33,132Binding:3096, Functional:24, ADMET:8, Toxicity:4
NPM1113Binding:108, Functional:5

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
FLT32.7.10.1receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
FLT33,132
NPM1113

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 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.

CompoundMax phaseCohort target (bioactivity)
PONATINIB4FLT3
AFATINIB4FLT3
FEDRATINIB4FLT3
TIVOZANIB4FLT3
AXITINIB4FLT3
SORAFENIB4FLT3
NERATINIB4FLT3
INFIGRATINIB PHOSPHATE4FLT3
INFIGRATINIB4FLT3
IBRUTINIB4FLT3
PALBOCICLIB4FLT3
REGORAFENIB4FLT3
ENTRECTINIB4FLT3
PACRITINIB4FLT3
FOSTAMATINIB4FLT3
QUIZARTINIB DIHYDROCHLORIDE4FLT3
CABOZANTINIB4FLT3
CERITINIB4FLT3, NPM1
VANDETANIB4FLT3
NILOTINIB4FLT3
BOSUTINIB4FLT3, NPM1
FILGOTINIB4FLT3
ABEMACICLIB4FLT3
BRIGATINIB4FLT3
PEXIDARTINIB4FLT3
PRALSETINIB4FLT3
PAZOPANIB4FLT3
NINTEDANIB4FLT3
SUNITINIB4FLT3

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2FLT3, NPM1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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: 4.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE13
PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04689815PHASE2UNKNOWNOral Arsenic Trioxide for NPM1-mutated AML
NCT05735184PHASE1RECRUITINGA Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
NCT06001788PHASE1RECRUITINGSafety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
NCT07566585PHASE1RECRUITINGDose Finding Study to Evaluate the Safety of BSB-2002 in Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients With NPM1 Mutation

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
AZACITIDINE41
GILTERITINIB41
QUIZARTINIB41
ZIFTOMENIB12
CHEMBL507519201
CHEMBL517398701

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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This page pulls from 72 datasets indexed by BioBTree:

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