title: Mutation of the p51/p63 gene is associated with blastic crisis in chronic myelogenous leukemia.
abstract: The p51/p63 gene, a novel member of the p53 gene family, has recently been identified at 3q27-9. There are at least six major isotypes of p51/p63 mRNA transcripts. p51A/TAp63gamma has the potential to induce apoptosis and growth suppression in a manner similar to p53, and other isotypes may suppress the p53 and p51A1TAp63gamma genes in a dominant-negative manner. We analyzed the mutation and expression of the p51/p63 gene in 80 cases of chronic myelogenous leukemia (CML) to evaluate its role in blastic transformation. Expression of the p51/p63 gene was detected in 74 cases. The alpha isotype of p51/p63 transcripts was dominantly expressed in 72 of these 74 cases. There was no correlation between the isotypes of p51/p63 transcripts and the clinical phase. Mutations of the p51/p63 gene were found in six cases. All these mutated cases expressed p51B/TAp63 alpha. In four of the six cases, the mutations were within a limited region (codon 151-170) corresponding to the DNA-binding domain. We hypothesized that this limited region is a hot spot for mutation of the p51/p63 gene. Mutations of the p53 gene were found in four cases of CML in blastic crisis (BC). Frequencies of the p51/p63 and p53 gene mutations were higher in BC (p51/p63 gene, 11.8%; p53 gene, 7.8%) than in the chronic phase (p51/p63 gene, 1.5%; p53 gene, 0%). The p51/p63 gene mutation may act similarly to the p53 gene mutation as a genetic alteration potentially responsible for the progression of CML.
authors.affiliation: Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Sakuma
authors.forename: K
authors.initials: K
authors.lastname: Dan
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: C081876:CKAP4 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012334:RNA, Neoplasm; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins