Mutation of the p51/p63 gene is associated with blastic crisis in chronic myelogenous leukemia

H. Yamaguchi, K. Inokuchi, Y. Sakuma, K. Dan

Research output: Contribution to journalArticle

26 Citations (Scopus)

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/TAp63γ has the potential to induce apoptosis and growth suppression in a manner similar to p53, and other isotypes may suppress the p53 and p51A/TAp63γ 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 α 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 α. 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 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.

Original languageEnglish
Pages (from-to)1729-1734
Number of pages6
JournalLeukemia
Volume15
Issue number11
DOIs
Publication statusPublished - 2001 Jan 1

Keywords

  • Blastic crisis
  • Chronic myelogenous leukemia
  • p51/p63 gene
  • p53 gene

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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