THE INCIDENCE AND PROGNOSTIC-SIGNIFICANCE OF MUTATIONS IN CODON-13 OFTHE N-RAS GENE IN ACUTE MYELOID-LEUKEMIA

To determine the incidence and prognostic significance of mutation in the N-ras gene in de novo acute myeloid leukemia (AML) we performed an analysis of bone marrow smears from 219 patients with de novo AML tre ated between 1984 and 1986 and followed for at least six years. DNA ex tracted from bone marrow smears taken at diagnosis was screened for th e presence of mutations in codons 12 and 13 of exon 1 by using the pol ymerase chain reaction to insert an Hph1 restriction enzyme site into DNA. Presumptive mutations were confirmed by direct sequencing. Mutati ons were detected in a total of 26 patients (12%); in nine patients (4 %) in codon 12 only, in ten patients (5%) in codon 13 only, and in sev en patients (3%) in both codons. Mutations in codon 12 or codon 13 wer e not associated with any clinical features. Mutations in codon 12 had no prognostic significance but mutations in codon 13 were associated with an increased durable remission, and a significantly which appeare d to he independent of other prognostic factors.