Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis

Abstract

Summary. Genomic DNA from patients with idiopathic myelofibrosis (IMF) was screened by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE) for mutations in the C‐KIT gene (60 patients), as well as the C‐FMS and FLT3 genes (40 patients). Intronic primers were used to amplify the entire coding region of both the C‐KIT and C‐FMS genes, and selected regions of the FLT3 gene. CSGE and direct DNA sequencing detected all previously reported as well as several novel polymorphisms in each of the genes. A novel c‐fms exon 9 mutation (Gly413Ser) was detected in two patients. Its functional significance remains to be determined. The c‐kit mutation Asp52Asn, previously described in two of six IMF patients in Japan, was not detected in this study. In addition, the reported c‐fms mutations involving codons 301 and 969 were not identified. Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis.