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NPM1 is the most common mutation in adult leukaemia. It moves a nuclear protein into the cytoplasm and, it turns out, makes the leukaemia dependent on menin.
NPM1 exon 12 frameshift mutations occur in ~30% of adult AML (50-60% of normal-karyotype AML). Favourable risk without FLT3-ITD (ELN 2022), but relapses are common and MRD by NPM1 transcript PCR is the best-validated molecular MRD marker in AML. NPM1-mutant blasts rely on the menin-KMT2A complex; revumenib (October 2025) and ziftomenib (November 2025) are approved for relapsed/refractory NPM1-mutated AML.
In plain words · NPM1 is the most common mutation in adult leukaemia. It moves a nuclear protein into the cytoplasm and, it turns out, makes the leukaemia dependent on menin.
NPM1 is the most common mutation in adult leukaemia. It moves a nuclear protein into the cytoplasm and, it turns out, makes the leukaemia dependent on menin.
Nucleophosmin is a nucleolar chaperone; the mutant acquires a nuclear export signal, delocalising to the cytoplasm and dysregulating HOX gene expression via menin-dependent chromatin binding.
1 product aims at NPM1 mutation: small molecules. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (NPM1 mutation) absent from normal cells. HPA NPM1: RNA low tissue specificity; high antibody staining in 45 normal tissues; highest cancer staining breast cancer (12 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Leukaemia); Open Targets associates it with 3 specific cancer types at or above 0.5 (non-small cell lung carcinoma, acute myeloid leukemia, dyskeratosis congenita); the corpus evidence decides and the Open Targets list is quoted for comparison. (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: NPM1 mutation label threshold; Human Protein Atlas NPM1 tissue; Open Targets ENSG00000181163 associations
First described 1986. Earliest sequence paper UniProt cites for the protein: Chan P.-K. et al, J. Biol. Chem, 1986, "Amino acid sequence of protein B23 phosphorylation site". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Nucleophosmin is a nucleolar chaperone; the mutant acquires a nuclear export signal, delocalising to the cytoplasm and dysregulating HOX gene expression via menin-dependent chromatin binding.
RNA: low tissue specificity, detected in all normal tissues.
HPA NPM1 tissue · HPA NPM1 pathology · HPA protein class: Essential proteins
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 30% | mutation | ~50-60% of cytogenetically normal AML |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Ziftomenib is the second menin inhibitor for leukaemia, approved in November 2025 as a once-daily pill for relapsed NPM1-mutated AML.
Query for this target: (TITLE:"NPM1 mutation" OR ABSTRACT:"NPM1 mutation" OR TITLE:"NPM1" OR ABSTRACT:"NPM1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NPM1 mutation, not a curated reading list.
Shares Menin inhibitor + venetoclax + azacitidine, MEIS1, HOXA9, AUGMENT-101 and the tag driver.
Shares MEIS1, HOXA9, Ziftomenib, FLT3.
Shares MEIS1, HOXA9, Ziftomenib, Revumenib.
Shares The undruggable drivers and the tag driver.
Shares AUGMENT-101, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Revumenib, Menin.
Shares Timothy J. Ley, Epigenetic reprogramming, Acute myeloid leukaemia and the tag driver.
Shares AUGMENT-101, Ziftomenib, Revumenib, Menin.
Shares AUGMENT-101, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Revumenib, Menin.