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Molecular genetic analisys of ASXL1, FLT3, KIT, NPM1, NRAS, TP53 and Wt1 mutations in acute myeloid leukemia patients 45–60 years old

[Original research]
Alexander Vladimirovich Vinogradov; Alexey Vasilievich Rezaykin; Sergey Vladimirovich Sazonov; Alexander Grigorievich Sergeev; Marina Yurievna Kapitonova;

The spectrum of ASXL1, FLT3, KIT, NPM1, NRAS, TP53 and WT1 genes mutations was studied in 55 middle aged patients (pts) with acute myeloid leukemia (AML) treated in hematological department since 2008 till 2018. Morphology of AML according to FAB-classification was as follows: M0 – 2, M1 – 3, M2 – 21, М3 – 9, M4 – 13, M4eo – 1, M5 – 1, M6 – 3, M7 – 1, AHL (myelo/lymphoblastic) – 1. Mutations were detected using automatic direct sequencing technique. The frequency of mutations in investigated proto- and antioncogenes was 36.7 %, including 2 cases (25.0 %) with favorable cytogenetics, 7 cases (23.8 %) with unfavorable cytogenetics, 9 cases (22.2 %) with normal karyotype and 2 cases (14.3 %) with unspecified cytogenetics. The frequency of mutations in NPM1 gene exons 9–12 was 22.9 %, NRAS gene exons 1–4 – 12.5 %, FLT3 gene exons 12–15 and 19–21 – 11.5 %, ASXL1 gene exons 12–13 – 11.1 %, KIT gene exons 7–12 and 16–19 – 6.5 %, WT1 gene exons 6–9 – 6.1 %, TP53 gene exons 4–11 – 2.6 %. Multiple genetic lesions were detected in 10.9 % specimens (usually NPM1 and FLT3 point mutations co-occurrence). As a result, detection of cryptic gene mutations was helped to clarify the prognostic stratification of AML in 18.2 % cases. Favorable prognosis of overall survival was established in 9 cases (16.4 %), intermediate – 15 (27.3 %), adverse –19 (34.5 %), unspecified –12 (21.8 %). These results indicate the priority of intensive induction polychemotherapy and allogenic bone marrow transplantation in the first remission as the main therapeutic technology in AML at the age of 45–60 years old.

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Keywords: acute myeloid leukemia, mutations, middle age, direct sequencing


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