ИССЛЕДОВАНИЕ СРЕДНЕГО ВОЗРАСТА ВОЗНИКНОВЕНИЯ ГЕННЫХ МУТАЦИЙ ПРИ ОСТРОМ МИЕЛОМОНОБЛАСТНОМ ЛЕЙКОЗЕ

Abstract

Aim: to determine the average age of occurrence of gene mutations in acute myelomonoblastic leukemia (AMML). Materials and methods. Bone marrow and peripheral blood samples from 40 patients (average age 50 years, including 13 aged 15 to 45 years, 15 aged 45-60 years, 12 aged over 60 years) with newly detected AMML were examined. Detection of chromosomal abnormalities was performed using standard cytogenetic and real-time polymerase chain reaction methods. Point mutations were screened in 8 genes: FLT3 (n=35), NPM1 (n=25), TP53 (n=24), C-KIT (n=23), NRAS (n=19), WT1 (n=18), DNMT3A (n=13), and KRAS (n=4) by direct automatic sequencing method. Results. The majority of patients (56.3%) had a normal karyotype, 15.6% had aneuploid karyotype, and 28.1% had other structural and quantitative chromosome abnormalities. 35.0% of patients had point mutations in the studied genes at the time of diagnosis of OMML. The highest mutation rates were found for the DNMT3A (30.8%), NPM1 (20.0%), and FLT3 (20.0%) genes. The frequency of double mutants was 15.2%. The average age of detection of mutations in the c-KIT and NPM1 genes corresponded to young adults (33.5±2.9 and 44.2±11.4, respectively), for 3 genes — to middle age (DNMT3A — 49.3±18.4; WT1 — 51.0; FLT3 — 54.0±12.3), for the TP53 gene — to the elderly (n=1, 63 years). The average age of double mutants was 42.2±13.7 years due to NPM1 and c-KIT co-mutations.