Mutations of the Ras Protooncogenes in Chronic Myelogenous Leukemia: A High Frequency of Ras Mutations in bcr/abl Rearrangement-Negative Chronic Myelogenous Leukemia

Abstract

Seventy cases of chronic myelogenous leukemia (CML) were analyzed for the presence of ras mutations using polymerase chain reaction (PCR), oligonucleotide hybridization, and direct PCR sequencing. All cases had preceding cytogenetic and bcr rearrangement studies. Aberrant ras genes were detected in none of 39 patients with Philadelphia (Ph) chromosome or bcr/abl rearrangement positive chronic-phase CML and in only 1 of 18 patients in blast crisis, suggesting that ras mutations have little or no role in initiation or progression of common CML. Seven of 13, or 54% of patients with bcr/abl rearrangement negative chronic phase CML (atypical CML) harbored mutations in ras, however. This high incidence of ras mutations, together with the absence of bcr/abl rearrangement, provides evidence that atypical CML is an entity that is molecularly distinct from common CML. Moreover, the clinical characteristics and the high frequency of ras mutations suggest that atypical CML may constitute a subset of the myelodysplastic syndrome and may be best classified as a variant of chronic myelomonocytic leukemia (CMML).