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Prognostic implication of FLT3 and Ras gene mutations in patients with acute promyelocytic leukemia (APL): a

C Callens1, S Chevret, J-M Cayuela

  • 1Department of Hematology, Hôpital Saint-Louis, Paris, France.

Leukemia
|May 13, 2005
PubMed

Insights

FLT3-ITD mutations in acute promyelocytic leukemia (APL) patients are linked to genetic instability and poor survival after relapse, despite not affecting initial remission rates.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Internal tandem duplications (ITDs) in the FLT3 gene occur in approximately 35% of acute promyelocytic leukemia (APL) cases.
  • The prognostic significance of FLT3-ITD in APL remains debated, contrasting with its established role in acute myeloid leukemia (AML) overall.

Purpose of the Study:

  • To investigate the incidence, clinical associations, and prognostic impact of FLT3-ITD, FLT3-D835 mutations, and Ras mutations in APL.
  • To clarify the role of these mutations in treatment outcomes and survival for APL patients.

Main Methods:

  • Analysis of 119 APL patients prospectively enrolled in APL-93 and APL-2000 trials.
  • Genotyping for FLT3-ITD, FLT3-D835 point mutations, and N-Ras/K-Ras mutations.

Main Results:

  • Mutation frequencies were 38% for FLT3-ITD, 20% for FLT3-D835, and 4% for Ras.
  • FLT3-ITD correlated with high white blood cell count, Sanz index, M3-variant subtype, and V/S PML-RAR alpha isoforms.
  • No significant impact of FLT3 or Ras mutations on complete remission, induction death, death in complete remission, or cumulative relapse incidence was observed.

Conclusions:

  • FLT3-ITD mutations in APL patients show a trend towards shorter overall survival, primarily due to significantly worse postrelapse survival.
  • This suggests underlying genetic instability in FLT3-ITD positive APL, potentially leading to acquisition of adverse mutations at relapse.

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