Analysis of granulocyte colony stimulating factor receptor isoforms, polymorphisms and mutations in normal...

Deletion mutants of the intracytoplasmic domain of the granulocyte colony stimulating factor receptor (G-CSFR) have shown that it contains a membrane-proximal region which must be conserved to allow the receptor to transduce a mitotic signal, and a C-terminal region necessary for transduction of cell differentiation. Changes in the intracytoplasmic domain may result in the uncoupling of these two processes, as in acute leukaemia, and such alterations could occur either as isoforms or mutations. We have studied the transmembrane domain and intracytoplasmic tail of the G-CSFR in RNA from blood or bone marrow of 11 haematologically normal controls and 40 patients with acute myeloid leukaemia (AML). Two novel transcripts of the receptor were identified, both were minor components and are unlikely to be of major physiological significance. We could find no evidence for altered levels of expression of these transcripts in the AML patients. In addition, only one point mutation was detected in the 40 patients screened by RT-PCR-SSCP, a C-->A substitution at nucleotide 2088 which changes a threonine to asparagine in the transmembrane domain and is probably a polymorphism. These results suggest that abnormalities in the G-CSFR are uncommon in AML.