title: Low frequency of ras oncogene mutations in Philadelphia-positive acute leukemia and report of a novel mutation H61 Leu in a single case.
abstract: Activating ras mutations are frequent (25-60%) in chronic myelomonocytic leukemia (CMML) and in acute myeloid leukemia (AML) (30%), in contrast to chronic myeloid leukemia (CML) in which the incidence is very low (0-3%). This might reflect that the leukemic cell in CML is at a level of differentiation in which ras gene activation is not involved or, alternatively, might be due to the presence in CML of the bcrlabl fused gene. We have analyzed the presence of point mutations in codons 12, 13, 59, 61 and 63 of N-, K-, and H-ras genes, in 26 cases of Philadelphia-chromosome-positive, bcrlabl-positive acute leukemia (Ph+ AL), and in eight CMML cases by using the polymerase chain reaction. Aberrant ras genes were detected in a single Ph+ AL case, and in four out of eight CMML patients. The Ph+ AL showing altered ras allele had an unusual point mutation in H-ras gene, substituting leucine for glutamine. This mutation has not been previously found in any hematological disease. Our findings suggest that ras mutations are probably not involved in the pathogenesis of those leukemias in which blast cells contain bcrlabl oncogene activation.
authors.affiliation: Academic Department of Hematology and Cytogenetics, Institute of Cancer Research, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: R
authors.initials: R
authors.lastname: Gill
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: S
authors.initials: S
authors.lastname: Levi
authors.forename: L M
authors.initials: LM
authors.lastname: Wiedemann
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
authors.forename: C J
authors.initials: CJ
authors.lastname: Marshall
mesh_terms: D003062:Codon; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D003062:Codon; D005973:Glutamine; D016044:Fusion Proteins, bcr-abl; D007930:Leucine