GENE MUTATIONS LANDSCAPE IN ADULT ACUTE MYELOMONOBLASTIC LEUKEMIA
DOI: 10.22138/2500-0918-2020-17-2-131-138
A.V. Vinogradov, A.V. Rezaykin, S.V. Sazonov, A.G. Sergeev
Sverdlovsk Regional Clinical Hospital N 1, Yekaterinburg, Russian Federation;
Ural State Medical University, Yekaterinburg, Russian Federation;
Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation
Abstract. Aim: to estimate gene mutations landscape in adult acute myelomonoblastic leukemia (AMML) patients (pts). Materials and methods. Bone marrow and peripheral blood samples were obtained from 40 AMML pts (including 13 aged 15 to 45, 15 aged 45-60, 12 aged over 60 years old), treated in Sverdlovsk Regional Hematological Centre during the period 2008–2019. Detection of chromosomal mutations performed using G-banding and real-time polymerase chain reaction. Gene mutation screening for 8 genes investigating the presence of FLT3 ITD and TKD, NPM1 exon 12 insertions, TP53 exons 4-11 mutations, as well as of mutations in c-KIT exons 7-12 and 16-19, NRAS exons 1-4, WT1 exons 6-9, DNMT3A exons 18-26 and KRAS exons 1-4 was performed using direct automatic sequencing. Results. The total frequency of FLT3, NPM1, TP53, C-KIT, WT1 and DNMT3A genes mutations in AMML was 35.0%. The most frequent mutations were detected in the DNMT3A (30.8%), NPM1 (20.0%), and FLT3 (20.0%) genes. Mutations in the RAS family genes were not detected, which may be due to the sample size. The frequency of double mutants was 15.2%, the average number of mutations per patient was 1.4, and mutations in the c-KIT, DNMT3A, NPM1 and FLT3 genes were most often co-operated. c-KIT and NPM1 genes mutations were mainly detected at a young patients, DNMT3A, WT1 and FLT3 — at a middle-aged patients and TP53 was identified in patient over 60 years old. The average age of the double mutants also corresponded to the young age (42,2) due to the predominance of mutations NPM1 and c-KIT.
Keywords: acute myelomonoblastic leukemia, mutations landscape, DNMT3A, FLT3, c-KIT, NPM1, TP53, WT1
Received 29.09.2020
For citation:
Vinogradov A.V., Rezaykin A.V., Sazonov S.V., Sergeev A.G. Gene mutations landscape in adult acute myelomonoblastic leukemia. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2020, Vol. 17, no. 2, pp. 131–138. DOI: 10.22138/2500-0918-2020-17-2-131-138 (In Russ)
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Authors
Alexander V. Vinogradov
Sverdlovsk Regional Clinical Hospital N 1, Department of Hematology
Hematologist, Dr. Sci. (Med.), Chief therapist of Sverdlovsk Regional Ministry of Health
34b, Wainer str., Yekaterinburg, Russian Federation, 620014
a.vinogradov@egov66.ru
Alexey V. Rezaykin
Ural State Medical University, Department of Medical Physics
Cand.Sci. (Med.), Professor assistant
3, Repin str., Yekaterinburg, Russian Federation, 620028
alexrez@usma.ru
Sergey V. Sazonov
Ural State Medical University, Department of Histology, Cytology and Embryology
Dr. Sci. (Med.), Professor, Chief of the department
3, Repin str., Yekaterinburg, Russian Federation, 620028
sazonov@usma.ru
Alexander G. Sergeev
Ural State Medical University, Department of Microbiology, Virology and Immunology
Dr. Sci. (Med.), Professor, Chief of the department
3, Repin str., Yekaterinburg, Russian Federation, 620028
sergeev@usma.ru