Rare occurrence of N-ras point mutations in Philadelphia chromosome positive chronic myeloid leukemia

Point mutations of the N-ras oncogene are relatively common in acute myelogenous leukemia (AML) cells, occurring in some 25% to 50% of patient samples. We used a technique involving the direct nucleotide sequencing of in vitro amplified N-ras genomic fragments to determine the frequency of N-ras point mutations in chronic myeloid leukemia (CML) cells at various stages of the disease. This approach will detect N-ras point mutations in a mixed population of cells if the mutation is present in 25% or more of the cells. We could not demonstrate any point mutation at N-ras codons 12,13 or 59–63 in any of the 44 CML cases analyzed, which included 21 blast crisis samples. In contrast with AML N-ras point mutations are exceedingly rare in CML.