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https://doi.org/10.14300/mnnc.2022.17086

The survey of the age dynamics of genetic and morphological variants of the acute myeloid leukemias

[Original research] [Internal diseases]
Alexander Vladimirovich Vinogradov; Alexey Vasilievich Rezaykin; Sergey Vladimirovich Sazonov; Evgeny Shchetinin; Dmitry Bobryshev; Alexander Grigorievich Sergeev;

The study includes the 257 patients with AML, 153 of them are 15–59 years old, 104 – aged 60 years and older. Screening of chromosomal mutations in leukemic blasts was performed using the standard cytogenetic method and real-time polymerase chain reaction, mutations in the c-KIT, FLT3, NPM1, NRAS and TP53 genes were detected by direct automatic mRNA sequencing. The predominant morphological variant of AML in the study group according to the FAB classification was M2 – 43.6 %. The statistically significant increasing in the proportion of acute myeloblastic leukemias (subtypes M1 and M2 according to FAB) was revealed in elderly and senile patients, and on the contrary, the decreasing in the frequency of acute promyelocytic leukemia (M3 according to FAB) was detected. The cytogenetic variant of AML was clarified in 82.1 % of the samples. The predominant variant was diploidy (39.8 %). Its frequency, along with AML with an unspecified karyotype, statistically significantly increased in the group of elderly and senile patients. The frequency of specific chromosomal mutations associated with a favorable prognosis was maximum in the group of patients, younger than 60 years (29.4 %), and on the contrary, decreased in 3.2 times in the older age. Gene mutations were detected in leukemic blasts at the stage of AML diagnosis in 34.2 % of patients: FLT3 17.1 %, NPM1 13.4 %, RAS 10.1 %, TP53 8.7 %, c-KIT 6.5 %. Age differences were determined for TP53 mutations, the frequency of which in the older age group increased by 13.5 times. с-KIT mutations, on the contrary, were detected 3.3 times more often in the age group of patients younger than 60 years. The frequency of double mutations was 6.3 % and did not change depending on age, which may be due to the limited sample size and the panel of studied genes.

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Keywords: acute myeloid leukemia, morphology, mutations, cytogenetics, sequencing, age