# NPM1 mutation

Source: https://onco.cc/targets/npm1/  
OnCo record `npm1` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Target
- Last checked: 2026-09-07
- Tags: driver; mrd-marker
- Symbol: NPM1
- Class: other
- 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.
- Where found: Adult AML (~30%); Normal-karyotype AML (50-60%)

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Nucleophosmin
- Wikipedia: https://en.wikipedia.org/wiki/Nucleophosmin

## Connected records

- targets: [FLT3](https://onco.cc/targets/flt3/), [HOXA9](https://onco.cc/targets/hoxa9/), [MEIS1](https://onco.cc/targets/meis1/), [Menin](https://onco.cc/targets/menin/)
- biomarkers: [NPM1 mutation](https://onco.cc/biomarkers/npm1-mutation/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/)
- drugs: [Revumenib](https://onco.cc/drugs/revumenib/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- terms: [ELN 2022 risk classification](https://onco.cc/terms/eln-risk/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/)
- trials: [AUGMENT-101](https://onco.cc/trials/augment-101/), [KOMET-001](https://onco.cc/trials/komet-001/)
- pairings: [Menin inhibitor + venetoclax + azacitidine](https://onco.cc/pairings/menin-plus-venetoclax-hma/)
- people: [Timothy J. Ley](https://onco.cc/people/timothy-ley/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- pathways: [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- key papers: [AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation](https://onco.cc/key-papers/paper-augment-101-revumenib-menin-nature-2023/)

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JSON: https://onco.cc/api/v1/entities/npm1.json