Expression of exogenous wt-p53 does not affect normal hematopoiesis: Implications for bone marrow purging

R. Scardigli, G. Bossi, G. Blandino, M. Crescenzi, S. Soddu, A. Sacchi

Research output: Contribution to journalArticle

Abstract

Some gene therapy approaches for cancer treatment attempt to transduce onco-suppressor genes into tumor cells. A central problem of this strategy is the targeting of tumor cells to avoid damage to normal ones. It has been noticed that transduction of wt-p53 into a large number of cancer cells induces tumor suppression. In contrast, some observations suggest that introduction of exogenous wt-p53 into nontransformed cells does not impair proliferation. If normal bone marrow (BM) cells are not affected by wt-p53 transduction, BM purging from p53-responding leukemic cells might be achieved in vitro by delivering the wild-type onco-suppressor to all marrow cells. We undertook a series of experiments to assess whether transduction of wt-p53 into normal hematopoietic cells is harmful. Two different wt-p53-recombinant retroviruses were used to infect primary, murine BM cells. Expression of exogenous wt-p53 in these cells did not affect in vitro colony formation, and did not induce any observable effects on morphology and differentiation. In contrast, the same viruses suppressed the tumor phenotype of v-src-transformed 32D cells. These results might open the way to gene therapy approaches to leukemias with the p53 gene without the need to target specifically and uniquely the tumor cells, sparing the normal ones.

Original languageEnglish
Pages (from-to)1371-1378
Number of pages8
JournalGene Therapy
Volume4
Issue number12
Publication statusPublished - 1997

Keywords

  • Gene therapy
  • Leukemia
  • Onco-suppressor
  • Retroviral vector
  • Tumor targeting

ASJC Scopus subject areas

  • Genetics

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