NPM1 mutation
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
Biology
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.
- Adult AML (~30%)
- Normal-karyotype AML (50-60%)
How common it is, by cancer
| 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.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetKMT2A (MLL) rearrangement
Shares AUGMENT-101, Menin inhibitor + venetoclax + azacitidine, ELN 2022 risk classification, AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation and the tag driver.
- TargetKRAS
Shares The undruggable drivers and the tag driver.
- TargetIDH1 / IDH2
Shares Timothy J. Ley, Epigenetic reprogramming, Acute myeloid leukaemia and the tag driver.
- TermDifferentiation syndrome
Shares AUGMENT-101, Ziftomenib, Revumenib, Menin.
- IdeaMenin inhibitors for infant KMT2A-rearranged ALL
Shares AUGMENT-101, Ziftomenib, Revumenib, Menin.
- PersonEunice S. Wang
Shares FLT3, Revumenib, Menin, Acute myeloid leukaemia.
- TargetBRAF
Shares The undruggable drivers and the tag driver.
- CompanyKura Oncology
Shares AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation, Ziftomenib, Acute myeloid leukaemia.