title: Activating point mutations in the betaC chain of the GM-CSF, IL-3 and IL-5 receptors are not a major contributory factor in the pathogenesis of acute myeloid leukaemia.
abstract: A number of mutant growth factor receptors have been described which are constitutively activated and confer factor independence on growth factor dependent cells, possibly through constitutive dimerization in the absence of ligand or induction of a conformational change. Mutations in receptor chains may therefore contribute to the pathogenesis of haemopoietic malignancies, for example by causing constitutive receptor activation or uncontrolled downstream signalling. Since most of the activated mutants reported for the betaC chain of the GM-CSF/IL-3/IL-5 receptor involve point mutations or truncations of the extracellular domain, we have analysed the coding sequence of this region using RT-PCR-SSCP of RNA from blast cells of 31 patients with acute myeloid leukaemia (AML). Two point mutations detected were silent, C301-->T (Cys91) and C1306-->T (Ser426). The latter had previously been identified with an allele frequency of 0.13 in the general population. Two further point mutations detected led to amino acid substitutions, G773-->C (Glu249Gln), which is equivalent to the mouse sequences, and G962-->A (Asp312Asn), both of which were found at similar frequencies in normal controls. Activating mutations of the betaC chain which might contribute to the pathogenesis of the disease are therefore rare in AML.
authors.affiliation: Department of Haematology, University College London Medical School.
authors.forename: R W
authors.initials: RW
authors.lastname: Freeburn
authors.forename: R E
authors.initials: RE
authors.lastname: Gale
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012334:RNA, Neoplasm / Q000032:analysis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D016185:Receptors, Interleukin-3 / Q000235:genetics*; D053649:Receptors, Interleukin-5; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D010446:Peptide Fragments; D012334:RNA, Neoplasm; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5