THE VALUE OF MUTATIONS IN THE ASXL1 GENE IN THE ONCOGENESIS OF ACUTE MYELOID LEUKEMIA IN ADULTS
DOI: 10.22138/2500-0918-2023-20-3-18-23
A.V. Vinogradov¹, S.V. Sazonov²,³
¹ State Autonomous Healthcare Institution of the Sverdlovsk Region
«Sverdlovsk Regional Clinical Hospital No. 1»,
Yekaterinburg, Russian Federation;
² State Autonomous Healthcare Institution of the Sverdlovsk Region
“Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”, Yekaterinburg, Russian Federation;
³ Federal State Budgetary Educational Institution of Higher Education
Ural State Medical University of the Ministry of Health of the Russian Federation, Yekaterinburg, Russian Federation
Abstract. The aim was to evaluate the significance of the ASXL1 gene mutations in the oncogenesis of acute myeloid leukemia (AML) in adults.
Materials and methods. Bone marrow and peripheral blood samples of 49 patients with AML aged from 18 to 84 years, treated at the Sverdlovsk regional hematological center, were examined, including those with a morphological variant of AML M0 – 3, M1 – 4, M2 – 19, M3 – 6, M4 – 10, M5 – 1, M6 – 1, M7 – 1, blast plasmacytoid dendritic cell neoplasm – 1, acute hybrid leukemia – 2, AML after chronic myeloproliferative disease (CMPD) – 2. Mutations in the ASXL1 gene were detected in peripheral blood and bone marrow samples by direct RNA sequencing (n=26) and high-throughput DNA sequencing (n=23) on automatic genetic analyzers ABI Prism 310 and MiSeqDX, respectively.
Results. It was found that pathogenetically significant mutations of the ASXL1 gene were detected in 16.3% of samples with AML M0, M2, M4, AML from CMPD and acute hybrid leukemia. The distribution of ASXL1 anomalies was as follows: deletion n. Del (1755;2007) — 4, duplication c.1934dupG — 3, non-synonymous transversion c.1348A>T — 1. Along with lesions of the ASXL1 gene, quantitative and structural chromosomal aberrations were determined in these samples, including del(5)(q13), t(8;21)(q22;q22), t(9;22)(q34;q11), as well as point mutations in the CEBPA, IDH2, NRAS, RUNX1, SRSF2, TET2 genes, internal tandem duplication in the FLT3 gene. This indicates the cooperation of two or more mutational events in the oncogenesis of ASXL1-positive AML, which can determine the different reaction of the tumor to chemotherapeutic treatment and the prognosis of the disease.
Keywords: mutation, acute myeloid leukemia, ASXL1 gene, oncogenesis, age
There is no conflict of interest.
Contact details of the corresponding author:
Alexander V. Vinogradov
a.vinogradov@egov66.ru
Received 12.07.2023
For citation:
Vinogradov A.V., Sazonov S.V. The value of mutations in the ASXL1 gene in the oncogenesis of acute myeloid leukemia in adults. [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2023, Vol. 20, no. 3, pp. 18–23. DOI: 10.22138/2500-0918-2023-20-3-18-23 (In Russ)
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Authors
Alexander V. Vinogradov
State Autonomous Healthcare Institution of the Sverdlovsk Region «Sverdlovsk Regional Clinical Hospital No. 1», Department of Hematology, Chemotherapy and Bone Marrow Transplantation
Hematologist, MD, chief therapist of Sverdlovsk Regional Ministry of Health
a.vinogradov@egov66.ru
Yekaterinburg, Russian Federation
Sergey V. Sazonov
State Autonomous Healthcare Institution of the Sverdlovsk Region “Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”,
Federal State Budgetary Educational Institution of Higher Education Ural State Medical University of the Ministry of Health of the Russian Federation,
MD, professor, chief of the department, deputy chief of the institute
prof-ssazonov@yandex.ru
Yekaterinburg, Russian Federation