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Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl

Gene Therapy volume 12, pages 541–545 (2005)Cite this article

Abstract

Antiangiogenic gene therapy offers an attractive approach to the treatment of a variety of malignancies, including those of the hematological system. However, evaluation of this approach has been hampered by the lack of appropriate animal models. We have recently produced transgenic mice expressing P230 bcr/abl that develop myeloproliferative disease (MPD) closely resembling human chronic myelogenous leukemia. Using this MPD murine model, we examined the feasibility of systemic antiangiogenic gene therapy for hematological malignancy. An adenoviral vector containing the secretable endostatin gene was injected into the right quadriceps muscle of the MPD mice. The increased endostatin level was detected for at least 6 months. Hematological parameters including platelet counts, granulocyte counts, and the hemoglobin concentration were improved by this gene therapy. Infiltration of megakaryocytes was also significantly inhibited in treated MPD mice. Reduction of the microvessel density was confirmed by histological examination. These results demonstrated, for the first time, that antiangiogenic gene therapy is effective to inhibit leukemogenesis caused by expression of the chimeric bcr/abl gene.

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Acknowledgements

We thank Dr Izumu Saito for generous provision of plasmids and Ad vector, Dr Tsutomu Igarashi for expert technical assistance and helpful discussion. This work was supported in part by grants from the Ministry of Health and Welfare of Japan and the Ministry of Education, Science, and Culture of Japan.

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  1. K Miyake and K Inokuchi: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan

    K Miyake, N Miyake & T Shimada

  2. Division of Gene Therapy Research, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan

    K Miyake, K Inokuchi, N Miyake & T Shimada

  3. Department of Internal Medicine, Division of Hematology/Oncology, Nippon Medical School, Tokyo, Japan

    K Inokuchi & K Dan

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  1. K Miyake
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  2. K Inokuchi
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Miyake, K., Inokuchi, K., Miyake, N. et al. Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl. Gene Ther 12, 541–545 (2005). https://doi.org/10.1038/sj.gt.3302427

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