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Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes

Talha Badar1, Keyur P Patel2, Philip A Thompson1

  • 1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Leukemia Research
|November 9, 2015
PubMed
Abstract

Insights

Detecting FLT3-ITD and RAS mutations during the myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) transformation indicates poorer outcomes. Patients with these mutations had significantly shorter survival post-transformation.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Myelodysplastic syndromes (MDS) transformation to acute myeloid leukemia (AML) involves complex molecular events.
  • The prognostic impact of specific mutations arising during MDS to AML progression is not fully understood.

Purpose of the Study:

  • To investigate the hypothesis that detecting FLT3-ITD and RAS mutations at MDS to AML transformation correlates with adverse outcomes.
  • To assess the prognostic significance of these mutations in patients progressing from MDS to AML.

Main Methods:

  • Analysis of 102 MDS patients with serial mutation testing (MDS and AML stages).
  • Inclusion criteria: wild-type FLT3-ITD and RAS at initial MDS diagnosis, progression to AML.
  • Focus on FLT3-Internal Tandem Duplication (ITD) and RAS pathway mutations.

Main Results:

  • FLT3-ITD and/or RAS mutations were detected in 26% of patients at AML transformation.
  • Patients with these mutations had a median survival of 2.4 months versus 7.5 months for wild-type.
  • Hazard ratio of 3.08 (95% CI: 1.9-5.0, p<0.0001) for poor outcome in mutated patients.

Conclusions:

  • FLT3-ITD and RAS mutations emerging during MDS to AML progression are significant independent predictors of poor prognosis.
  • Early detection of these mutations may guide therapeutic strategies and patient counseling.
Keywords:
AMLFLT3-ITDLeukemic transformationMDSRAS

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