Mutation analysis of the N‐ras proto‐oncogene in active and remission phase of human acute leukemias

Abstract

DNA isolated from blood or bone‐marrow samples from 18 patients with acute non‐lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N‐ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT → GAT transitions in codon 12 and one CAA → AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow‐up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N‐ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N‐ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.