Определение молекулярно-генетического профиля у взрослых больных острыми миелоидными лейкозами методом секвенирования нового поколения

Introduction . Acute myeloid leukaemia (AML) is associated with multiple driver mutations, which prognostic value remains understudied. Aim . Assessment of the frequency of mutations in various genes and their impact on acute myeloid leukaemia outcome in adults. Materials and methods . The study included 90 adult patients with newly diagnosed AML; 76 were aged under 60, 14 were 60 and more years old. Patients under 60 had chemotherapy (CT) “7+3” as induction, the elder cohort had variant low-dose CT with hypomethylating agents. The molecular genetic status of patients was determined using next-generation sequencing; the in-house gene panel included ASXL1, BCOR, DNMT3, FLT3, IDH1, IDH2, PIGA, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53 and U2AF2 . Results . Nucleotide substitutions were identified in genes DNMT3, TET2, TP53, SETBP1, BCOR, RUNX1, IDH2, IDH1, FLT3, U2AF2, SF3B1 in 57.8 % of the patients ( n = 52), with 17.8 % ( n = 16) having compound mutations in two or three genes. Treatment efficacy and long-term outcomes were assessed against age, ELN-2017 risk groups and mutations in genes TP53, RUNX1, IDH1, IDH2 and DNMT3 . In the long term, a reliable variation was revealed in the overall survival (OS) rate with respect to mutations in genes TP53 and RUNX1 . Patients with mutant TP53 had 30 % OS, those with the intact gene — 53.4 % (p = 0.0037). Similar results were obtained with RUNX1 : mutations marked 20 % OS, intact patients had 54% OS ( p = 0.0466). Conclusion . Mutations in genes FLT3 -ITD, NPM1 and CEBPA are proxy to AML. However, a more accurate prognosis and optimal choice of therapy require detailed molecular profiling due to genetic heterogeneity of AML patients.