N-RAS oncogene mutations in patients with agnogenic myeloid metaplasia in leukemic transformation

From 5% to 20% of patients with agnogenic myeloid metaplasia (AMM) will evolve into a terminal leukemic phase; N-RAS gene mutations are the most common gene abnormalities detected in patients with leukemia. The present study was designed to see if N-RAS gene mutations are associated with the leukemic transformation in AMM. Over a 9 year period, in a single institution, 43 patients with AMM were studied. Of these, ten patients were found to be in leukemic phase. The results showed that none of the patients in chronic phase (40 patients) had N-RAS gene mutations, while two patients in leukemic phase showed this gene mutation. One patient was found to have a codon 12 mutation with arginine substituting for glycine (GGT-->CGT); the other was a codon 12 mutation with glutamine substituting for glycine (GGT-->GAT). The present study suggests that N-RAS mutations are rare events in the chronic phase of AMM, and are only occasionally found when patients have evolved into leukemic transformation. Further studies to search for other gene abnormalities in AMM may be warranted.