{"entity":{"id":"paper-falini-npm1-nejm-2005","kind":"paper","name":"Cytoplasmic nucleophosmin in acute myeloid leukaemia with a normal karyotype","aka":[],"tldr":"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.","asOf":"2026-09-17","links":[{"label":"N Engl J Med 2005","url":"https://doi.org/10.1056/NEJMoa041974"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15659725/"}],"tags":[],"related":[],"cancers":["aml-npm1-kmt2a"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2005,"doi":"10.1056/NEJMoa041974","pmid":"15659725","authors":"Falini B, Mecucci C, Tiacci E, et al.","paperType":"translational","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."],"whatItMeans":"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."],"changedPractice":true,"participants":591},"route":"/key-papers/paper-falini-npm1-nejm-2005/","neighbours":{"cancer":[{"id":"aml-npm1-kmt2a","kind":"cancer","name":"NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia","route":"/cancers/aml-npm1-kmt2a/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}