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Blastic Crisis of CML

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

Leukemia volume 15, pages 1729–1734 (2001)Cite this article

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 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.

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Acknowledgements

We thank Dr H Nishi, Department of Obstetrics and Gynecology, Tokyo Medical College, for his useful discussions.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

    H Yamaguchi, K Inokuchi & K Dan

  2. Department of Oral and Maxillofacial Surgery II, Nippon Dental University, Tokyo, Japan

    Y Sakuma

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  2. K Inokuchi
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  3. Y Sakuma
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Yamaguchi, H., Inokuchi, K., Sakuma, Y. et al. Mutation of the p51/p63 gene is associated with blastic crisis in chronic myelogenous leukemia. Leukemia 15, 1729–1734 (2001). https://doi.org/10.1038/sj.leu.2402265

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