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

5 Citations (Scopus)

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

p53 Genes
Genetic Therapy
Leukemia
Bone Marrow Purging
Splenomegaly
Retroviridae
Subcutaneous Injections
Tumor Suppressor Genes
Acute Myeloid Leukemia
Intravenous Injections
Neoplasms
Bone Marrow
Kidney
Lung
Mortality
Liver

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.

Development of a murine orthotopic model of leukemia : Evaluation of TP53 gene therapy efficacy. / Bossi, Gianluca; Scardigli, Raffaella; Musiani, Piero; Martinelli, Roberta; Gentileschi, Maria Pia; Soddu, Silvia; Sacchi, Ada.

In: Cancer Gene Therapy, Vol. 7, No. 1, 2000, p. 135-143.

Research output: Contribution to journalArticle

Bossi, G, Scardigli, R, Musiani, P, Martinelli, R, Gentileschi, MP, Soddu, S & Sacchi, A 2000, 'Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy', Cancer Gene Therapy, vol. 7, no. 1, pp. 135-143.
Bossi G, Scardigli R, Musiani P, Martinelli R, Gentileschi MP, Soddu S et al. Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy. Cancer Gene Therapy. 2000;7(1):135-143.
Bossi, Gianluca ; Scardigli, Raffaella ; Musiani, Piero ; Martinelli, Roberta ; Gentileschi, Maria Pia ; Soddu, Silvia ; Sacchi, Ada. / Development of a murine orthotopic model of leukemia : Evaluation of TP53 gene therapy efficacy. In: Cancer Gene Therapy. 2000 ; Vol. 7, No. 1. pp. 135-143.
@article{66873f400ff141dba52154182c505027,
title = "Development of a murine orthotopic model of leukemia: Evaluation of TP53 gene therapy efficacy",
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.",
keywords = "Bone marrow, Leukemia, gene therapy, TP53",
author = "Gianluca Bossi and Raffaella Scardigli and Piero Musiani and Roberta Martinelli and Gentileschi, {Maria Pia} and Silvia Soddu and Ada Sacchi",
year = "2000",
language = "English",
volume = "7",
pages = "135--143",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Development of a murine orthotopic model of leukemia

T2 - Evaluation of TP53 gene therapy efficacy

AU - Bossi, Gianluca

AU - Scardigli, Raffaella

AU - Musiani, Piero

AU - Martinelli, Roberta

AU - Gentileschi, Maria Pia

AU - Soddu, Silvia

AU - Sacchi, Ada

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Bone marrow

KW - Leukemia, gene therapy

KW - TP53

UR - http://www.scopus.com/inward/record.url?scp=0033953529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033953529&partnerID=8YFLogxK

M3 - Article

C2 - 10678366

AN - SCOPUS:0033953529

VL - 7

SP - 135

EP - 143

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 1

ER -