Prognostic Importance of Mutations in the rus Proto-Oncogenes in De Novo Acute Myeloid Leukemia

Mutations of the Nand K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12,13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells. ras mutations were detected by an algorithm based on allelespecific oligonucleotide hybridization. Eighteen of 99 (1 8%) patients harbored mutations in either Nor K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both Nand K-ras (N = 3). There were no significant differences between ras-negative and