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.
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.
Green
Claire
C
Department of Haematology, Cancer Institute, University College London, London, UK.
Linch
David C
DC
Gale
Rosemary E
RE
D000483:Alleles; D016022:Case-Control Studies; D020440:Gene Duplication; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3