AGE-RELATED FEATURES OF TP53 GENE MUTATIONS IN ACUTE MYELOBLASTIC LEUKEMIA PATIENTS
DOI:10.22138/2500-0918-2024-21-1-33-39
A.V. Vinogradov¹, S.V. Sazonov²,³
¹Sverdlovsk Regional Clinical Hospital N 1, Yekaterinburg, Russian Federation;
²Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation;
³Ural State Medical University, Yekaterinburg, Russian Federation
Abstract.
The aim of the study was to characterize the frequency of TP53 gene mutations in acute myeloblastic leukemia (AML) in the age aspect. Materials and methods. 116 AML patients aged 15 to 84 years, who were observed at the Sverdlovsk Regional Hematology Center, were studied. The study included patients with the following morphological variants of AML: M1 — 12, M2 — 66, M4 — 32, M4eo — 3, M5 — 3. Detection of point mutations in the TP53 gene was performed in peripheral blood samples and bone marrow aspirate by direct total RNA sequencing (n=96) and next-generation DNA sequencing (n=20) on automatic genetic analyzers ABI Prism 310 and MiSeqDx, respectively. Results. It was found that clinically significant mutations of the TP53 gene were detected in 8.6% of cases with morphological variants of AML M2 and M4. In 8 cases, they were represented by non-synonymous substitutions. Deletion of n. Del(645) and tandem duplication were observed each in 1 sample, respectively. TP53 double mutations were detected in 2 observations. Cytogenetic analysis of samples with mutations in the TP53 gene most often (n=8) revealed complex karyotype anomalies involving 3 or more chromosomes, less often — a normal or unspecified karyotype (according to one observation). Statistically significant dynamics of the frequency of TP53 gene mutations was revealed depending on the age of patients. In the subgroup of AML patients younger than 45 years, TP53 mutations were not detected, in middle-age patients their frequency was 5.6%, and at the age of 60 years and older — 15.4%. The revealed dynamics of the TP53 mutation frequency may determine the different chemosensitivity of leukemic cells and the prognosis of AML in different age groups of patients.
Keywords:
mutation, TP53 gene, acute myeloblastic leukemia, age
There is no conflict of interest.
Contact details of the corresponding author:
Alexander V. Vinogradov
a.vinogradov@egov66.ru
Received 19.02.2024
For citation:
Vinogradov A.V., Sazonov S.V. Age-related features of TP53 gene mutations in acute myeloblastic leukemia patients. [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2024, Vol. 21, no. 1, pp. 33–39. DOI:10.22138/2500-0918-2024-21-1-33-39 (In Russ)
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Authors
Alexander V. Vinogradov
Sverdlovsk Regional Clinical Hospital N 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
Ural State Medical University, Department of Histology, Cytology and Embryology, Institute of Medical Cell Technologies
MD, professor, chief of the department, deputy chief of the institute
prof-ssazonov@yandex.ru
Yekaterinburg, Russian Federation