Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy


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Abstract

Detection of FLT3 gene mutations in acute myeloid leukemia is now recognized as an unfavorable factor that affects the disease course, emerging the risk of relapses and overall survival shortening and disease-free survival of patients. The aim of the study was to determine the frequency of mutations of the gene FLT3 and to assess their impact on clinical indicators, overall survival and disease-free survival in patients with acute myeloid leukemia. We compared complete blood count parameters, karyotype, duration of overall survival and disease-free survival in 199 patients with acute myeloid leukemia depending on the presence or absence of mutations of the FLT3 gene. Significant differences across these groups were discovered only in WBC and blasts between the group of patients with acute myeloid leukemia (FLT3+) and without mutations in the FLT3 gene (FLT3-). The differences between two groups were also identified in patients chromosomal aberrations. Significant differences (p=0,00024) in the duration of overall survival between groups of patients with acute myeloid leukemia with mutations of FLT3-ITD+, FLT3-TKD+ and FLT3- were demonstrated. Median overall survival was: 1 6 months for patients with mutation FLT3-ITD+ and 17 months for FLT3-TKD+ patients and not achieved for FLT3- patients. The use of modern molecular genetic methods of research in acute myeloid leukemia allows to improve the diagnosis of the disease, as well as to carry out risk stratification and individualize therapy. The use of targeted therapy for FLT3-positive patients who are not candidates for hematopoietic stem cell transplantation will increase the effectiveness of the treatment and improve the performance of overall survival and disease-free survival.

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About the authors

A. M Radzhabova

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

Email: aradzhabova91@gmail.com

S. V Voloshin

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency; S.M. Kirov Military Medical Academy; I.I. Mechnikov North-Western State Medical University

I. S Martynkevich

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

A. A Kuzyaeva

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

VA. Shuvaev

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

E. V Motyko

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

A. Y Kuvshinov

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

M. S Fominykh

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

A. V Schmidt

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

L. B Polushkina

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

M. P Bakay

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

S. A Tiranova

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

M. N Zenina

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

N. A Potihonova

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

SA. Kudryashova

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

V. A Balashova

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

J. V Chubukina

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

O. S Uspenskaya

Leningrad Regional Clinical Hospital

E. V Karyagina

City Hospital № 15, Saint Petersburg

A. N Bogdanov

S.M. Kirov Military Medical Academy

A. V Chechetkin

Russian scientific research Institute of Hematology and Transfusiology of Federal medical-biological Agency

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