Prevalence and Clinical Significance of FLT3 Mutation Status in Acute Myeloid Leukemia Patients: A Multicenter Study

Arch Med Res. 2016 Apr;47(3):172-9. doi: 10.1016/j.arcmed.2016.06.003. Epub 2016 Jun 30.

Abstract

Background and aims: FLT3-ITD mutations in acute myeloid leukemia (AML) are associated with a poor prognosis. In Latin America, little epidemiological data exist about these mutations and their influence on clinical evolution and prognosis. Standardization and well-established clinical correlation make FLT3 mutational analysis by molecular methods an invaluable tool to decide among treatment options and to determine AML prognosis.

Methods: We assessed the prevalence of FLT3-ITD mutations in 138 patients with AML at four hematology referral centers from Mexico and Colombia. Molecular methods based on polymerase chain reaction (PCR) were employed for determining FLT3-ITD status.

Results: Mutations were present in 28 patients indicating a prevalence of 20.28%. Median age was 47 years (5-96). The FLT3 mutation positive group was older, had higher WBC and hemoglobin values and lower platelet counts but without statistical significance. A not previously described mutation in the FLT3 gene was found in one patient involving a nucleotide exchange of timine for cytosine at the 66608 position. A high mortality was found in the FLT3-mutated group, 67.8 vs. 42.72% in the non-mutated group and median survival was 4.9 months vs. 20.4 months, p = 0.009. A mutated FLT3 did not confer poor prognosis to those with M3 AML. The mutated FLT3 population had poor overall survival (OS) despite hematoprogenitor stem cell transplantation (HSCT).

Conclusion: Prevalence of FLT3-ITD mutation in AML was present in a proportion comparable to other populations and, when present, was associated with a very poor prognosis.

Keywords: AML; Acute myeloid leukemia; FLT3; Latin America.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / enzymology*
  • Male
  • Mexico
  • Middle Aged
  • Mutation
  • Prognosis
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism*

Substances

  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3