Structural aberrations of genes associated with leukemogenesis in patients with acute myeloid leukemia of intermediate prognosis

Introduction. The development of therapy resistance and relapses of acute myeloid leukemia (AML), especially in the intermediate prognosis group, may be due to the molecular genetic heterogeneity of tumor cells. Chromosomal microarray analysis (CMA) can detect microdeletions, duplications, and copy-neutral loss of heterozygosity (cnLOH) which may be associated with a response to therapy. Aim: to evaluate tthe frequency of copy number aberrations and cnLOH in leukemogenesis-associated genes in patients with intermediate-stage AML and and their relationship to survival and response to treatment. Materials and methods . The study included 35 patients with de novo AML from the intermediate prognosis group for ELN2017. Copy number analysis by CMA was performed for a panel of 36 genes associated with leukemogenesis. The reference group included 102 healthy individuals without oncohematological disorders who also underwent comparable CMA testing. Results. Genomic aberrations were detected in 91.18 % of patients, most often in the genes of chromatin modifiers (64.7 % patients) and tumor suppressor genes (64.7% patients). The cnLOH type (PHF6, SMC1A, BKORL1) prevailed. KMT2A duplications occurred only in AML patients — 14.3 % (p < 0.001) and were associated with worse survival (log-rank P = 0.05). Combinations of genomic alterations involving 4–7 functional gene groups were found in 20.6% of patients. Conclusion. Driver gene aberrations, especially KMT2A duplications, are associated with an unfavorable clinical outcome in AML with an intermediate prognosis.