title: N-RAS activation in the terminal stage of undifferentiated chronic myeloproliferative disease.
abstract: The relationship between activation of the N-RAS gene and the leukemic progression of undifferentiated chronic myeloproliferative disease (UCMPD) was investigated in a 71-year-old male. Hematologically, it was difficult to differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR rearrangement (BCR-) either at the beginning or in the terminal stages of the disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular analysis, using the polymerase chain reaction (PCR) and direct sequencing. The DNA of leukemic cells at the beginning of the leukemic progression did not show any abnormalities, but at the terminal stage of the disease the DNA showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon 13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These observations suggest that the activated N-RAS gene contributes to the hematologic progression of UCMPD.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inokuchi
authors.forename: M
authors.initials: M
authors.lastname: Futaki
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Kuwabara
authors.forename: T
authors.initials: T
authors.lastname: Shinohara
authors.forename: K
authors.initials: K
authors.lastname: Dan
authors.forename: T
authors.initials: T
authors.lastname: Nomura
mesh_terms: D000368:Aged; D002454:Cell Differentiation; D002908:Chronic Disease; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015321:Gene Rearrangement; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction