NPM1 mutation

aka NPM1 mutation, NPM1-mutated AML, NPM1c, mutated NPM1, NPM1 type A, NPM1mut

NPM1 mutations, found in about a third of adult acute myeloid leukaemias, misplace the nucleophosmin protein into the cytoplasm. They mean a better outlook without FLT3-ITD, a sensitive MRD marker, and since 2025 a targeted menin inhibitor.

Frameshift insertions in NPM1 exon 12 (type A, TCTG, in about 80 percent) are detected by PCR or sequencing and the transcript is tracked as measurable residual disease. Ziftomenib (Komzifti, 2025) is labelled for relapsed or refractory AML with a susceptible NPM1 mutation and no satisfactory alternative; revumenib (Revuforj) gained an NPM1-mutated relapsed or refractory indication in 2025 alongside its KMT2A-rearranged one. NPM1-mutated AML without FLT3-ITD is favourable-risk in ELN 2022 and is often spared transplant in first remission if MRD clears.

Part ofNPM1 mutation· NPM1 All readouts

NPM1 mutation: what it is and how drugs act on it · animated schematic, not to scale

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.

Sequencing 2 approval thresholds

What it means for a patient

An NPM1 mutation at diagnosis is, on its own, good news: these leukaemias respond well to chemotherapy, and the mutation can be tracked in your blood to catch relapse early. If the leukaemia does come back, ziftomenib or revumenib tablets are on label. Whether you also have a FLT3-ITD changes the plan, so both results are read together.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

An NPM1 exon 12 frameshift insertion (type A, B, D or other) by PCR or sequencing of blood or marrow; quantitative PCR of the mutant transcript is used for residual disease.

“KOMZIFTI is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options”
Komzifti prescribing information

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
Susceptible NPM1 mutation, relapsed or refractory	Ziftomenib	NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia	FDA	label
NPM1 mutation, relapsed or refractory	Revumenib	NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia	FDA	label

Drugs whose label names it

Ziftomenib Revumenib

Tests that measure it

FoundationOne Heme NeoGenomics NeoTYPE profiles

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.