ANALYSIS OF GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR ISOFORMS, POLYMORPHISMS AND MUTATIONS IN NORMAL HEMATOPOIETIC-CELLS AND ACUTE MYELOID-LEUKEMIA BLASTS

Deletion mutants of the intracytoplasmic domain of the granulocyte col ony stimulating factor receptor (G-CSFR) have shown that it contains a membrane-proximal region which must be conserved to allow the recepto r 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 acu te leukaemia, and such alterations could occur either as isoforms or m utations, We have studied the transmembrane domain and intracytoplasmi c tail of the G-CSFR in RNA from blood or bone marrow of 11 haematolog ically normal controls and 40 patients with acute myeloid leukaemia (A ML). Two novel transcripts of the receptor were identified, both were minor components and are unlikely to be of major physiological signifi cance. We could find no evidence for altered levels of expression of t hese transcripts in the AML patients. In addition, only one point muta tion was detected in the 40 patients screened by RT-PCR-SSCP, a C --> A substitution at nucleotide 2088 which changes a threonine to asparag ine in the transmembrane domain and is probably a polymorphism. These results suggest that abnormalities in the G-CSFR are uncommon in AML.