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1: Leukemia. 2008 May;22(5):951-5. Epub 2008 Feb 14.
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NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features.

Andersen MT, Andersen MK, Christiansen DH, Pedersen-Bjergaard J.

Department of Clinical Genetics, Hematology/Oncology Section 4052, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. morten.tolstrup.andersen@rh.regionh.dk

Frameshift mutations of the nucleophosmin gene (NPM1) were recently reported as a frequently occurring abnormality in patients with de novo acute myeloid leukemia (AML). To evaluate the frequency of NPM1 mutations in patients with therapy-related myelodysplasia (t-MDS) and therapy-related AML (t-AML), and their possible association to type of previous therapy and to other gene mutations, 140 patients with t-MDS or t-AML were analyzed for mutations of NPM1. NPM1 mutations were observed in 7 of 51 patients presenting as overt t-AML, as compared to only 3 of 89 patients presenting as t-MDS (P=0.037). The mutations were not related to any specific type of previous therapy, but they were significantly associated with a normal karyotype and mutations of FLT3 (P=0.0002 for both comparisons). Only 1 of 10 patients with NPM1 mutations presented chromosome aberrations characteristic of therapy-related disease, and 7q-/-7, the most frequent abnormalities of t-MDS/t-AML, were not observed (P=0.002). This raises the question whether some of the cases presenting NPM1 mutations were in fact cases of de novo leukemia. The close association to class I mutations and the inverse association to class II mutations suggest mutations of NPM1 as representing a class II mutation-like abnormality in AML.

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PMID: 18273044 [PubMed - indexed for MEDLINE]