FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype


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Abstract

Aim. To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML).
Materials and methods. The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied.
Results. Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1- and FLT3-ITD+/ NPM1- genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-ITD mutation on EFS.
Conclusion. The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM1- genotypes to be identified as a poor prognosis group.

About the authors

Irina Stepanovna Martynkevich

Email: genetics.spb@mail.ru

Sergey Vasil'evich Gritsaev

Mikhail Viktorovich Moskalenko

Marina Petrovna Ivanova

Vasilisa Yur'evna Aksenova

Sof'ya Aleksandrovna Tiranova

Kudrat Mugutdinovich Abdulkadyrov

I S Martynkevich

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

S V Gritsayev

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

M V Moskalenko

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

M P Ivanova

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

V Yu Aksenova

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

S A Tiranova

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

K M Abdulkadyrov

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

Russian Research Institute of Hematology and Transfusion, Federal Biomedical Agency

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Copyright (c) 2010 Martynkevich I.S., Gritsaev S.V., Moskalenko M.V., Ivanova M.P., Aksenova V.Y., Tiranova S.A., Abdulkadyrov K.M., Martynkevich I.S., Gritsayev S.V., Moskalenko M.V., Ivanova M.P., Aksenova V.Y., Tiranova S.A., Abdulkadyrov K.M.

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