title: Analysis of the coding sequence for the GM-CSF receptor alpha and beta chains in patients with juvenile chronic myeloid leukemia (JCML).
abstract: Peripheral blood granulocyte-macrophage progenitors (CFU-GMs) from patients with juvenile chronic myeloid leukemia (JCML) are able to proliferate spontaneously in the absence of exogenous growth factors and studies have shown that these progenitors display a hypersensitive growth response to GM-colony-stimulating factors (CSFs) in culture. We screened RNA from six patients with JCML for mutations in the GM-CSF receptor (GM-CSFR) coding sequence using RT-PCR-SSCP. Altered patterns were found in five patients for the GM-CSFR alpha chain, and in five patients for the beta chain. Two nucleotide substitutions accounted for all alpha chain abnormalities; one was conservative for Val333 and the other caused an Ala17-->Gly substitution. Both had previously been detected in normal controls. Sequencing of beta chain abnormalities revealed four base substitutions. Three were previously described polymorphisms, one causing a Pro603-->Thr substitution and two conservative point mutations involving Ser426 and Pro648. A further nucleotide mutation, which resulted in a Glu249-->Gln substitution, was also found but is not thought to be of pathological significance. Polymorphisms of the GM-CSFR alpha and beta chains are common, but pathogenic point mutations of the GM-CSFR are infrequent in patients with JCML and are unlikely to be involved in the hypersensitivity to GM-CSF demonstrated by progenitor cells.
authors.affiliation: Department of Haematology, Univeristy College London Medical School, UK.
authors.forename: R W
authors.initials: RW
authors.lastname: Freeburn
authors.forename: R E
authors.initials: RE
authors.lastname: Gale
authors.forename: H M
authors.initials: HM
authors.lastname: Wagner
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D017421:Sequence Analysis
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor