NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

• Published in: Leukemia Vol. 22; no. 5; pp. 951 - 955
• Main Authors: Andersen, M T, Andersen, M K, Christiansen, D H, Pedersen-Bjergaard, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2008; Nature Publishing; Nature Publishing Group
• Subjects: Abnormalities; Acute myeloid leukemia; Aged; Aged, 80 and over; Biological and medical sciences; Cancer Research; Care and treatment; Chromosome aberrations; Chromosomes; Critical Care Medicine; Diagnostic Errors; DNA Mutational Analysis; Female; fms-Like Tyrosine Kinase 3 - genetics; Frameshift mutation; Gene Frequency; Gene mutations; Genes; Health aspects; Hematologic and hematopoietic diseases; Hematology; Humans; Intensive; Internal Medicine; Karyotypes; Kinases; Leukemia; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Molecular Epidemiology; Mutant Proteins; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Neoplasms, Second Primary - diagnosis; Neoplasms, Second Primary - genetics; Nuclear Proteins - genetics; Oncology; original-article; Patients; Proteins; Signal transduction; Therapy; United States; Denmark; Germany; mutations of NPM1; therapy-related AML; therapy-related MDS; Acute myelogenous leukemia; Treatment; Hematology; NPM1 gene; Genetics; Malignant hemopathy; Mutation; therapy- related AML; Myelodysplastic syndrome; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2008.17

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.