Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy (original) (raw)

Cancer Gene Therapy volume 7, pages 135–143 (2000)Cite this article

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.

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Authors and Affiliations

  1. Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute - Centro Richerche Sperimentali, Rome, Italy
    Gianluca Bossi, Raffaella Scardigli, Roberta Martinelli, Maria Pia Gentileschi, Silvia Soddu & Ada Sacchi
  2. Department of Oncology and Neurosciences, “G. D'Annunzio” University, Chieti, Italy
    Piero Musiani

Authors

  1. Gianluca Bossi
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  2. Raffaella Scardigli
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  3. Piero Musiani
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  4. Roberta Martinelli
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  5. Maria Pia Gentileschi
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  6. Silvia Soddu
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  7. Ada Sacchi
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Correspondence toSilvia Soddu or Ada Sacchi.

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Bossi, G., Scardigli, R., Musiani, P. et al. Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy.Cancer Gene Ther 7, 135–143 (2000). https://doi.org/10.1038/sj.cgt.7700101

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