FLT-3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact

Br J Haematol. 2004 May;125(4):463-9. doi: 10.1111/j.1365-2141.2004.04935.x.

Abstract

FLT-3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation-loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT-3 aberrations in a cohort of APL patients. FLT-3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT-3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT-3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT-3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT-3 ITD to be associated with non-remission (P = 0.06). For disease-free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT-3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT-3 inhibitors in the treatment of APL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Cohort Studies
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / immunology
  • Leukemia, Promyelocytic, Acute / mortality
  • Leukocyte Count
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Sex Factors
  • Survival Rate
  • Tandem Repeat Sequences

Substances

  • Membrane Proteins
  • flt3 ligand protein