DNMT3A co-mutation is required for FLT3-ITD as an adverse prognostic indicator in intermediate-risk cytogenetic group AML. Issue 8 (3rd August 2018)

• Record Type: Journal Article
• Authors: Ma, Juan; Dunlap, Jennifer; Paliga, Aleksandra; Traer, Elie; Press, Richard; Shen, Lisong; Fan, Guang
• Is Part Of: Leukemia & lymphoma. Volume 59:Issue 8(2018)
• Page Start: 1938
• Page End: 1948
• Publication Date: 2018-08-03
• Subjects: Myeloid leukemias and dysplasias -- cytogenetics -- molecular genetics; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2017.1397659
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: This single institution cohort study of 132 AML patients investigated the clinical implications of co-mutations detected with a 42-gene NGS panel. In the intermediate-risk cytogenetic group, FLT3-ITD is an adverse prognostic indicator only in the presence of a DNMT3A co-mutation, regardless of NPM1 mutation status. In the absence of a concomitant DNMT3A mutation, there was no significant difference in overall survival between FLT3-ITD positive and FLT3-ITD negative patients. Furthermore, mutation analysis on post-induction specimens showed that residual FLT3-ITD and/or DNMT3A mutations were associated with a high frequency of therapy resistance or relapse in AML. While FLT3-ITD positive patients are currently considered high risk, incorporation of DNMT3A mutation status may be needed to refine prognostication and guide clinical management in AML. Multi-gene mutation testing is essential to provide novel insights related to diagnostic and prognostic information.