Abstract:

Objective To investigate the roles of FLT3-ITD and DNMT3A mutations in the prognosis of acute myeloid leukemia（AML） patients in intermediate-risk-cytogenetic-group. Methods A total of 132 de novo AML patients were enrolled from the Affiliated Hospital of Oregon Health and Science University from 2010 to 2016,and they were classified into favorable-risk-cytogenetic-group（24 cases）,intermediate-risk-cytogenetic-group（79 cases） and adverse-risk-cytogenetic-group（27 cases）. There were 2 cases with unknown cytogenetic information. Totally,42 genes being relevant to hematopoietic malignancies were determined by next generation sequencing（NGS）. Results There were 91%（120/132） of AML cases with at least one mutation,and the pattern of co-mutations（≥2） accounted for 61%. Kaplan-Meier analysis demonstrated that the overall survival in FLT3-ITD mutation positive group for intermediate-risk-cytogenetic-group had statistical significance with that in FLT3-ITD mutation negative group（P<0.001）. When DNMT3A was co-mutated,FLT3-ITD mutation positive group had a shorter overall survival compared to FLT3-ITD mutation negative group（P<0.001）. In the present of DNMT3A wildtype,there was no statistical significance for overall survival between FLT3-ITD mutation positive and FLT3-ITD mutation negative groups（P>0.05）. FLT3-ITD mutation positive with DNMT3A mutation group had a shorter overall survival compared to FLT3-ITD mutation negative group（P<0.001） and FLT3-ITD mutation positive with DNMT3A wildtype group（P=0.003）. Conclusions In intermediate-risk-cytogenetic-group,the co-mutations of FLT3-ITD and DNMT3A have an adverse prognosis. The determinations of FLT3-ITDand DNMT3A mutations may be needed to refine prognostication and guide clinical management in AML.

Key words: FLT3-ITD gene, DNMT3A gene, Mutation, Acute myeloid leukemia, Prognostic factor