Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation

M. G. Rizzo, A. Zepparoni, B. Cristofanelli, R. Scardigli, M. Crescenzi, G. Blandino, S. Giuliacci, S. Ferrari, S. Soddu, A. Sacchi

Research output: Contribution to journalArticle

Abstract

Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53(Val135) mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.

Original languageEnglish
Pages (from-to)1429-1438
Number of pages10
JournalBritish Journal of Cancer
Volume77
Issue number9
Publication statusPublished - 1998

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Keywords

  • Apoptosis
  • Differentiation
  • Gene therapy
  • Leukaemia
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rizzo, M. G., Zepparoni, A., Cristofanelli, B., Scardigli, R., Crescenzi, M., Blandino, G., Giuliacci, S., Ferrari, S., Soddu, S., & Sacchi, A. (1998). Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation. British Journal of Cancer, 77(9), 1429-1438.