DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE
https://doi.org/10.20538/1682-0363-2015-1-18-23
Abstract
Aim: to estimate the frequency of DNMT3A gene exons 18–26 point mutations in acute myeloid leukemia (AML) patients (pts) using target automatic sequencing technique.
Material and Methods. Bone marrow and peripheral blood samples were obtained from 34 AML pts aged 21 to 64, who were treated in Sverdlovsk Regional Hematological Centre (Ekaterinburg) during the period 2012–2014. Distribution of the pts according to FAB-classification was as follows: AML M0 – 3, M1 – 1, M2 – 12, M3 – 3, M4 – 10, M5 – 2, M6 – 1, M7 – 1, blastic plasmacytoid dendritic cell neoplasm – 1. Total RNA was extracted from leukemic cells and subjected to reverse transcription. DNMT3A gene exons 18–26 were amplified by PCR. Detection of mutations in DNMT3A gene was performed by direct sequencing. Sequencing was realized using an automatic genetic analyzer ABI Prism 310.
Results. The average frequency of functionally significant point mutations in DNMT3A gene exons 18– 26 among the treated AML pts was 5.9%. They were detected in morphological subgroups M2 and M4(according to WHO classification). The average frequency of DNMT3A gene exons 18–26 point mutations among the AML M2 and M4 pts without chromosomal aberrations and TP53 gene point mutations was 14.3%. In both cases there were samples in which DNMT3A gene mutations were accompanied by molecular lesions of NPM1, KRAS and WT1 genes. AML pts with DNMT3A gene exons 18–26 point mutations characterized by poor response to standard chemotherapeutic regimens and unfavorable prognosis.
About the Authors
A. V. Vinogradov
Sverdlovsk Regional Ministry of Health, Ekaterinburg; Ural State Medical University, Ekaterinburg
Russian Federation
Vinogradov Alexander V.
Russian Federation
Vinogradov Alexander V.
A. V. Rezaykin
Sverdlovsk Regional Ministry of Health, Ekaterinburg; Ural State Medical University, Ekaterinburg
Russian Federation
Rezaykin Alexey V.
Russian Federation
Rezaykin Alexey V.
A. G. Sergeev
Sverdlovsk Regional Ministry of Health, Ekaterinburg; Ural State Medical University, Ekaterinburg
Russian Federation
Sergeev Alexander G.
Russian Federation
Sergeev Alexander G.
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Review
For citations:
Vinogradov A.V., Rezaykin A.V., Sergeev A.G. DNMT3A GENE POINT MUTATIONS DETECTION IN ACUTE MYELOID LEUKEMIA PATIENTS USING SEQUENCING TECHNIQUE. Bulletin of Siberian Medicine. 2015;14(1):18-23. (In Russ.) https://doi.org/10.20538/1682-0363-2015-1-18-23
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