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Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia

Fabio P S Santos1, Dan Jones, Wei Qiao

  • 1Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Cancer
|April 28, 2011
PubMed
Abstract

Insights

FMS-like tyrosine kinase 3 (FLT3) mutations impact survival in normal karyotype acute myeloid leukemia (AML), particularly FLT3-internal tandem duplications. High FLT3-ITD burden worsens outcomes in NK-AML patients.

Area of Science:

  • Hematology
  • Oncology
  • Genetics

Background:

  • The prognostic significance of FMS-like tyrosine kinase 3 (FLT3) mutations and mutation burden in cytogenetic subgroups of acute myeloid leukemia (AML) remains incompletely understood.
  • Investigating these factors in non-normal karyotype (NK) AML is crucial for risk stratification.

Purpose of the Study:

  • To evaluate the impact of FLT3 mutations and mutation burden on survival outcomes across different cytogenetic subgroups of AML patients.
  • To determine the prognostic value of FLT3-internal tandem duplication (ITD) and FLT3-tyrosine kinase domain (TKD) mutations in AML.

Main Methods:

  • Newly diagnosed AML patients were stratified into three cytogenetic subgroups: core binding factor (CBF) AML, NK-AML, and poor-risk AML.
  • Analysis included the frequency of FLT3 mutations (ITD and TKD) and their correlation with event-free survival (EFS) and overall survival (OS).
  • Multivariate analysis was performed to assess the independent prognostic value of FLT3 mutations.

Main Results:

  • FLT3 mutations were detected in 20% of CBF-AML, 32% of NK-AML, and 7.6% of poor-risk AML patients.
  • FLT3 mutations did not significantly impact EFS in CBF-AML or poor-risk AML.
  • In NK-AML, FLT3-ITD mutations were associated with significantly worse EFS (20 weeks vs. 41 weeks; P < .00,001), while FLT3-TKD mutations did not show a significant impact (61 weeks vs. 41 weeks; P = .15).
  • Higher FLT3-ITD mutation burden correlated with worse EFS and OS in NK-AML patients.
  • Multivariate analysis confirmed FLT3-ITD as a negative prognostic factor for EFS in NK-AML (HR, 3.1; P = .03).

Conclusions:

  • FLT3 mutations lack prognostic impact in AML patients with good-risk (CBF) and poor-risk karyotypes.
  • FLT3-ITD mutations portend a worse survival in patients with NK-AML.
  • The negative prognostic effect of FLT3-ITD mutations in NK-AML is exacerbated by a high mutation burden.

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