Most acute myeloid leukaemia patients with intermediate mutant FLT3/ITD levels do not have detectable bi-allelic disease, indicating that heterozygous disease alone is associated with an adverse outcome

Br J Haematol. 2008 Jul;142(3):423-6. doi: 10.1111/j.1365-2141.2008.07196.x. Epub 2008 Jun 3.

Abstract

FLT3 internal tandem duplication mutant levels >50%, indicative of bi-allelic disease in some cells, are associated with a particularly poor prognosis in acute myeloid leukaemia; lower levels have an intermediate prognosis relative to wild-type FLT3. To examine whether a small population of homozygous mutant cells is responsible for the worse relapse risk rather than heterozygous disease per se, we determined the genetic composition of 34 intermediate mutant level (25-50%) samples. Only two had evidence of mutant homozygosity; only one had more homozygous than heterozygous mutant cells. Bi-allelic disease in intermediate mutant level cases is uncommon and heterozygous disease is sufficient for adverse outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Gene Duplication
  • Heterozygote
  • Homozygote
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / genetics*
  • Prognosis
  • Recurrence
  • Tandem Repeat Sequences*
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

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