Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy

Gianluca Bossi, Raffaella Scardigli, Piero Musiani, Roberta Martinelli, Maria Pia Gentileschi, Silvia Soddu, Ada Sacchi

Research output: Contribution to journalArticle

Abstract

The onco-suppressor gene TP53 has potential use in the gene therapy of many human cancers including leukemias. The latter indication derived from numerous experimental reports of p53-mediated suppressing effects on human and murine leukemia cells in vitro. However, few in vivo experiments have been performed, and those that have used a subcutaneous injection of p53- transduced leukemia cells. Thus, we developed an orthotopic leukemia model in adult, syngenic mice to evaluate the feasibility of TP53-mediated therapeutic approaches. We found that among other cells, v-src-transformed 32D myeloid progenitors induce leukemia when injected intravenously in syngenic mice. The resulting malignancy resembles the clinical manifestations of human acute myeloid leukemia because it is characterized by a massive invasion of bone marrow compartments, splenomegaly, generalized lymphadenopathy, and a macroscopic or microscopic infiltration of the kidneys, liver, and lungs. When these 32Dv-src cells were infected with a TP53-recombinant retrovirus before intravenous injection, we found a decreased mortality and, in those animals that develop leukemia, a drastic reduction of the generalized organ infiltration, suggesting that exogenous TP53 expression might be used for ex vivo bone marrow purging from leukemia cells.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalCancer Gene Therapy
Volume7
Issue number1
Publication statusPublished - 2000

    Fingerprint

Keywords

  • Bone marrow
  • Leukemia, gene therapy
  • TP53

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Bossi, G., Scardigli, R., Musiani, P., Martinelli, R., Gentileschi, M. P., Soddu, S., & Sacchi, A. (2000). Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy. Cancer Gene Therapy, 7(1), 135-143.