Study of the Age Dynamics of Morphological Subtypes of Acute Myeloid Leukemia in Adults

Abstract

Aim: to determine the age dynamics of morphological subtypes of acute myeloid leukemia in adult patients. Materials and methods. The study group consisted of 132 patients (including 34 aged 15 to 45 years, 46 aged 45-60 years, 52 aged over 60 years) with newly diagnosed AML. Patients with acute promyelocytic leukemia were not included in the study. The diagnosis was made in accordance with WHO recommendations and FAB classification criteria. In all cases, morphological verification was performed, including cytological, cytochemical studies and immunophenotyping. Detection of chromosomal abnormalities was performed using standard cytogenetic and real-time polymerase chain reaction methods. Point mutations were screened in 7 genes: c-KIT, DNMT3A, FLT3, NRAS, NPM1, TP53 and WT1 by direct sequencing method. Results. The distribution of morphological variants of AML according to the FAB classification was as follows: M2 — 47.7%, M4 — 26.5%, M1 — 7.6%, M0 — 4.5%, M6 — 4.5%, M5 — 3.0%, M4eo — 2.3%, blastic plasmacytoid dendritic cell neoplasm — 1.5%, acute myelofibrosis — 0.8%, acute hybrid leukemia — 0.8%. Complex genetic abnormalities were detected in 18.2%, specific chromosome abnormalities associated with a favorable prognosis — 7.6%, specific chromosome abnormalities associated with an unfavorable prognosis — 5.3%, normal cytogenetics — 28.8%. Mutations in the FLT3 gene were detected in 15.0%, NPM1 — 14.3%, DNMT3A — 12.5%, NRAS — 12.2%, TP53 — 9.6%, c-KIT — 5.7%, WT1 — 4.2%. It was revealed that the frequency of acute myeloid leukemias with monocytic differentiation (M4, M4eo and M5 according to FAB) had a statistically significant tendency to decrease with increasing age: in the subgroup of patients younger than 45 years, it was 44.1%, in the age of 45-60 years — 32.6%, in the age of 60 years and older — 23.1%. These differences correlated with the age-related dynamics of the frequency of genetic abnormalities in AML, including a decrease in the frequency of NPM1 gene mutations and specific chromosomal aberrations, as well as an increase in the frequency of TP53 abnormalities in older age groups.