FLT3 and its role in the pathogenesis of acute myeloid leukaemia.
FLT3, a tyrosine kinase receptor class III (RTK), and its ligand (FL) are important for normal haematopoiesis and the development of the immune system. Recently, internal tandem duplications (FLT3 ITDs) in exons 14 and/or 15 that lead to constitutive receptor activation, have been described in 20-25% of adults with acute myeloid leukaemia (AML). The FLT ITD mutations, which are thought to disrupt a repressor sequence in the juxta-membrane region, confer a poor prognosis in AML, especially in patients under the age of 60 years. Furthermore, FLT3 "activating loop" mutations involving exon 20 have been reported in 7% of AML cases, making FLT3 the most commonly mutated gene in AML. FLT3, therefore, is a potentially important molecular target for AML therapy and already phase I clinical trials have been initiated.
Reilly
John T
JT
Molecular Haematology Unit, Division of Molecular and Genetic Medicine, M floor, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. j.t.reilly@sheffield.ac.uk
D000208:Acute Disease; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology* / Q000235:genetics; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051941:fms-Like Tyrosine Kinase 3
D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3