ABSENCE OF N-RAS MUTATIONS IN MYELOID AND LYMPHOID BLAST CRISIS OF CHRONIC MYELOID-LEUKEMIA

Mutations within N-ras oncogene codons 12, 13, and 61 occur in approxi mately 25-30% of patients with acute nonlymphocytic leukemia and at a lower frequency (6-20%) in patients with acute lymphocytic leukemia. M oreover, N-ras mutations have been described in patients with chronic myeloid leukemia (CML) in blast crisis but have not been observed duri ng the chronic phase of the disease. In view of the morphological and clinical similarities between acute leukemia and the blast crisis of C ML, the question was raised whether the presence of N-ras mutations is associated with the phenotype of acute leukemia. We investigated leuk emic cells from 100 patients with CML for the presence of N-ras mutati ons in the mutational hot spot codons. The cases analyzed included 87 diagnosed with different types of blast crisis and 13 cases in acceler ated or chronic phase of the disease. Fragments from N-ras exons I and II containing the codons of interest were amplified by polymerase cha in reaction and analyzed for the presence of point mutations by three different technical approaches, including specific oligonucleotide hyb ridization, direct sequencing, and single-strand conformation polymorp hism analysis. N-ras mutations were not detected in any of the CML pat ients investigated. Only one patient, in whom the initial diagnosis of CML-blast crisis had been revised to chronic myelomonocytic leukemia, displayed an N-ras mutation within codon 13. Our data strongly sugges t that N-ras mutations do not play a role in myeloid or lymphoid blast crisis of CML.