DNMT3A co-mutation is required for FLT3-ITD as an adverse prognostic indicator in intermediate-risk cytogenetic group AML

Juan Ma, Jennifer Dunlap, Aleksandra Paliga, Elie Traer, Richard Press, Lisong Shen, Guang Fan

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Nov 23 2017

Keywords

  • cytogenetics
  • molecular genetics
  • Myeloid leukemias and dysplasias

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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