N-ras gene mutations in childhood acute non-lymphoblastic leukemia

In view of the potential role for ras activation in leukemogenesis, we have screened a number of children with acute non-lymphoblastic leukemia (ANLL) for activating point mutations at codons 12, 13 and 61 of the N-ras proto-oncogene using panels of oligonucleotide probes in conjunction with polymerase chain reaction (PCR) gene amplification. In contrast to the frequent occurrence (approximately 30%) of N-ras mutation reported in adult ANLL, 6 of 46 cases (13%) at the time of diagnosis had N-ras mutations involving codons 12 and 13. In these patients we also determine whether presenting clinical symptoms, cellular pathology, karyotype, or eventual outcome distinguished them from the ras-negative group. N-ras activation tended to be associated with a higher white blood cell count at diagnosis (mean of 225,000/microliters vs 91,000/microliters) and fewer remissions obtained after 28 days of therapy (3/6, 50% vs 24/32, 75%). It is possible that activation of N-ras oncogene may be involved in the progression of some cases of childhood ANLL.