ras Mutations in Preleukaemia, in Patients Following Cytotoxic Therapy and in Normal Subjects

Abstract

Point mutations in members of the RAS gene family, NRAS, KRAS and HRAS, are a common molecular lesion in patients with acute myeloid leukaemia (AML). Approximately 30% of such patients show mutations (Bos, 1987; Farr et al., 1988) mostly in NRAS, although KRAS abnormalities are also seen. Mutations in HRAS are a rare abnormality in haemopoietic malignancies (Browett et al., 1989). A similar pattern of mutations is also seen in patients with the preleukaemic Myelodysplastic syndromes (MDS), where mutations have been detected in up to 41% of patients (Padua et al., 1988; Yunis et al., 1989). In MDS RAS mutation appears to be associated with poor prognosis in terms of an increased likelihood of transformation to acute leukaemia, and whilst RAS mutation can be detected in all subtypes of MDS (Padua et al., 1988), the highest incidence is seen those patients a monocytic phenotype (Padua et al., 1988; Yunis et al., 1989).