title: Role of p53 in leukemogenesis of chronic myeloid leukemia.
abstract: This review attempts to provide current information on the role played by the p53 gene in normal and leukemic hematopoiesis with particular emphasis on chronic myeloid leukemia. On the basis of the currently available data we can argue that p53 acts as a negative regulator of proliferation of myeloid mature cells and CD34+ progenitors, and its action is mediated through changes in cell cycle kinetics, mainly before the S phase. The p53-dependent pathway is also regulated by several proteins, including p16, p21, p27 (cyclin-dependent kinase [CDK] inhibitors), and a few oncogenes (bcl-2, bax, MDM-2). Although there is some information about the changes in the p53 gene seen in various types of leukemia, the functions and biological importance of these changes in the pathogenesis of leukemia are still largely elusive. During the past several years, accumulated evidence suggests that changes in the p53 gene are commonly associated with blast crisis of chronic myeloid leukemia (CML) but rarely with chronic phase, and they are represented by rearrangements, deletions and point mutations. As for most of the tumors, the majority of point mutations occur between exons 4 and 8 (hot regions). In patients with CML in blastic crisis the most frequent mechanism of p53 inactivation is complete deletion of one allele in association with a point mutation in the remaining allele.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institute of Hematology, University of Ferrara, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lanza
authors.forename: S
authors.initials: S
authors.lastname: Bi
mesh_terms: D016158:Genes, p53; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics
chemical_list: D016376:Oligonucleotides, Antisense