Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Acta Haematol DOI: 10.1159/000339506 Prognostic Impact of NPM1 Mutations in Serbian Adult Patients with Acute Myeloid Leukemia Milos Kuzmanovic c Natasa Tosic a Natasa Colovic d Teodora Karan-Djurasevic a Vesna Spasovski a Milena Radmilovic a Gordana Nikcevic a Nada Suvajdzic-Vukovic b, d Dragica Tomin b, d Ana Vidovic b, d Marijana Virijevic d Sonja Pavlovic a Milica Colovic b a Institute of Molecular Genetics and Genetic Engineering, and b Medical Faculty, University of Belgrade, c Department of Hematology, Mother and Child Healthcare Institute ‘Dr. Vukan Cupic’, and d Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia found in this study can be assigned to a small cohort of ana- lyzed AML patients, as can the presence of FLT3 and IDH mu- tations or other genetic lesions that cooperate with NPM1 mutations influencing prognosis. Copyright © 2012 S. Karger AG, Basel Introduction Acute myeloid leukemia (AML) is a highly heteroge- neous group of hematological malignancies. AML pa- tients are categorized into prognostic groups according to their karyotype. However, about 45% of AML patients have no microscopically detectable chromosome abnor- malities. This subset of AML is called AML with a normal karyotype (NK-AML). Recently, a number of genetic mu- tations and changes in gene expression have been identi- fied in this cytogenetic subset of AML [1, 2]. These new genetic markers showed substantial prognostic relevance and revealed an amazing heterogeneity of this, previously considered to be uniform, group of patients [3]. Nucleophosmin (NPM), encoded by the NPM1 gene, is a ubiquitously expressed nucleolar protein that continu- Key Words Acute myeloid leukemia  FLT3 mutations  IDH mutations  NPM1 mutations Abstract Based on current findings, the presence of NPM1 mutations in acute myeloid leukemia (AML) patients is associated with an increased probability of complete remission (CR) and bet- ter overall survival (OS). We determined the incidence and prognostic relevance of NPM1 mutations, their association with FLT3 and IDH mutations, and other clinical characteris- tics in Serbian adult AML patients. Samples from 111 adult de novo AML patients, including 73 AML cases with a normal karyotype (NK-AML), were studied. NPM1, FLT3, and IDH mu- tations were detected by PCR and direct sequencing. NPM1 mutations were detected in 22.5% of patients. The presence of NPM1 mutations predicted a low CR rate and shorter OS. NPM1 mutations showed an association with both FLT3 and IDH mutations. Survival analysis based on NPM1/FLT3 muta- tional status revealed a lower OS for NPM1 + /FLT3 – compared to the NPM1 – /FLT3 – group in NK-AML patients. The lack of impact or unfavorable prognostic effect of NPM1 mutations Received: December 20, 2011 Accepted after revision: May 15, 2012 Published online: $$$ Natasa Tosic, PhD Laboratory for Molecular Hematology Institute of Molecular Genetics and Genetic Engineering Vojvode Stepe 444a, RS–11010 Belgrade (Serbia) Tel. +381 11 39 76 445, E-Mail nmtosic  @  sezampro.rs © 2012 S. Karger AG, Basel 0001–5792/12/0000–0000$38.00/0 Accessible online at: www.karger.com/aha AHA339506.indd 1 AHA339506.indd 1 31.07.2012 14:48:58 31.07.2012 14:48:58