Comprehensive analysis of mutations and clonal evolution patterns in a cohort of patients with cytogenetically normal acute myeloid leukemia

Abstract Background Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability, clonal selection and evolution leukemic clones during treatment. We performed high throughput exome sequencing matched presentation relapsed samples from 6 cytogenetically normal AML (CN-AML) patients treated standard remission induction chemotherapy in order contribute investigation mutational landscape CN-AML Result A total 24 32 variants were identified relapse respectively an average 4.0 per patient at 5.3 relapse, SNVs being more frequent than indels both disease stages. All have least one gene that frequently mutated most these classic recurrent hotspot including NPM1 p.W288fs, FLT3 -ITD, NRAS p.G12D IDH2 p.R140Q. In addition, we found two distinct patterns relapse: (1) a clone acquires evolves into after chemotherapy; (2) persists without addition novel mutations. Conclusions The findings this study suggest relapse-initiating may pre-exist prior therapy, harbor or acquire confer selective advantage chemotherapy, resulting expansion eventually leading relapse.