High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG).

By way of a Next-Generation Sequencing NGS high throughput approach, we defined the mutational profile in a cohort of 221 normal karyotype acute myeloid leukemia (NK-AML) enrolled into a prospective randomized clinical trial, designed to evaluate an intensified chemotherapy program for remission induction.NPM1,DNMT3A,andFLT3-ITD were the most frequently mutated genes whileDNMT3A,FLT3,IDH1,PTPN11, andRAD21mutations were more common in theNPM1mutated patients (p< 0.05).IDH1R132H mutation was strictly associated withNPM1mutation and mutually exclusive withRUNX1andASXL1. In the whole cohort of NK-AML, no matter the induction chemotherapy used, by multivariate analysis, the achievement of complete remission was negatively affected by theSRSF2mutation. Alterations ofFLT3(FLT3-ITD) andU2AF1were associated with a worse overall and disease-free survival (p< 0.05).FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar toFLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.