N-ras Mutations in Acute Myelogenous Leukemia: A Review of the Current Literature and an update of the Southwest Oncology Group Experience

Point mutations of the N-ras proto-oncogene have been frequently detected in samples of acute myelogenous leukemia (AML). In general the N-ras point mutation has been found in approximately 25% of samples, with some studies detecting the mutation in as many of 60% of samples. In this report we review the current literature regarding N-ras mutations in AML with emphasis on the updated experience of the Southwest Oncology Group (SWOG). The SWOG study examined 55 adult AML patients prospectively enrolled in a treatment protocol and found N-ras point mutations in 8 of 55 patients (15%). These mutations were usually in codon 12, 13 or 61, but one patient had mutations in both codons 13 and 61, and another had an unusual point mutation in N-ras codon 60. The presence of the N-ras mutation was not associated with pre-treatment clinical variables, response to induction therapy, or survival, except for a higher percentage of FAB M4 subtypes among mutation-positive patients. In this paper we compare the SWOG experience to the aggregate of literature regarding N-ras mutations in AML. In general while the N-ras mutation is common in AML, there is no clear evidence that it is sufficient or necessary for leukemic transformation. The presence of the N-ras mutation in AML does not seem to identify a unique clinical subset of AML patients.