# Cytoplasmic nucleophosmin in acute myeloid leukaemia with a normal karyotype

Source: https://onco.cc/key-papers/paper-falini-npm1-nejm-2005/  
OnCo record `paper-falini-npm1-nejm-2005` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

This study discovered that about a third of acute myeloid leukaemias, and most with normal chromosomes, carry a mutation in the NPM1 gene that displaces its protein into the cytoplasm, defining a distinct and relatively favourable form of the disease.

## Summary

Immunohistochemical and sequencing study of 591 AML cases showing cytoplasmic nucleophosmin in 35 percent, almost always caused by mutations in exon 12 of NPM1, concentrated in normal-karyotype AML (about 50 to 60 percent), associated with monocytic features, CD34 negativity and a good response to induction chemotherapy in the absence of FLT3-ITD.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2005
- DOI: 10.1056/NEJMoa041974
- Authors: Falini B, Mecucci C, Tiacci E, et al.
- Findings: Cytoplasmic NPM1 in 35.2 percent of primary AML and in the majority of normal-karyotype cases.; Associated with higher complete remission rates and mutual exclusivity with recurrent translocations.
- What it means: NPM1-mutated AML is now its own WHO category. The mutation is a stable target for measurable residual disease monitoring and the disease is one of the two indications for menin inhibitors.
- Caveats: Prognostic benefit is lost when FLT3-ITD is co-mutated at high allelic ratio.; Discovery study; clinical management implications developed over the following decade.

## Sources

- N Engl J Med 2005: https://doi.org/10.1056/NEJMoa041974
- PubMed: https://pubmed.ncbi.nlm.nih.gov/15659725/

## Connected records

- cancers: [NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia](https://onco.cc/cancers/aml-npm1-kmt2a/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

---
JSON: https://onco.cc/api/v1/entities/paper-falini-npm1-nejm-2005.json