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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