Comparative characteristics of quantitative and structural chromosome abnormalities at the time of diagnosis and in relapses of acute myeloid leukemias

Abstract

Acute myeloid leukemias (AML) are a heterogeneous group of neoplasms of hematopoietic tissue, to determine the subtypes of which cytomorphological and cytochemical methods, immunophenotyping, cytogenetic and molecular genetic studies are carried out. Numerous genetic studies have identified criteria for diagnosis and prognosis of the course of the disease, which play a decisive role in the algorithms for stratifying clinical risk groups, which in turn contributes to the choice of optimal treatment tactics. However, the effectiveness of chemotherapy may lose its importance due to the lack of response to therapy and the development of relapses. The aim of the work was to establish ways to form resistance to therapy by comparing the features of quantitative and structural chromosome abnormalities at the time of diagnosis and in relapse of AML. Karyotyping was performed on bone marrow cells of 14 patients at the time of diagnosis of AML, sex ratio 1.0:1.0, mean age 44.0±3.6 years and 9 patients in relapsed disease: sex ratio 1.0:0.8, mean age 31.0±5.9 years. The analysis of the results included a comparison of the features of karyotype formation by clone structure, assessment of clones in relation to ploidy, balanced and unbalanced structural rearrangements and the frequency of chromosome involvement in such rearrangements. Subsequently, the formation of the stages of clonal chromosome abnormalities evolution was reconstructed and the frequencies of the cytogenetic prognosis groups were compared. As a result of the studies, the heterogeneity of quantitative (monosomies, trisomies) and structural balanced (translocations, inversions, insertions) and unbalanced chromosome abnormalities (deletions, isochromosomes, additional material of unknown origin, marker chromosomes) were determined, both in diagnosis and in relapse of AML. Mosaic karyotypes were almost three times more likely to occur in relapses than at the time of diagnosis (100% vs. 35.7%). At the time of diagnosis, an increased percentage of hyperdiploid clones (28.6%) was registered due to trisomies of chromosomes 2, 8×2, 13, 19, 20 and complex karyotypes (21.4%); chromosome 17 (20.8%) was more often involved in structural rearrangements, the group of intermediate cytogenetic prognosis dominated (57.1%). In relapses, chromosomes 8 and 9 were more often involved in structural rearrangements (17.6% each) and the group of unfavorable cytogenetic prognosis dominated (55.6%).