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Animal Models

Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice

Leukemia volume 15, pages 814–818 (2001)Cite this article

Abstract

We have developed an in vivo model of differentiated human acute myeloid leukemia (AML) by retroviral infection of the cytokine-dependent AML cell line TF-1 with the v-Src oncogene. When injected either intravenously or intraperitoneally into 300 cGy irradiated SCID mice, animals formed multiple granulocytic sarcomas involving the adrenals, kidneys, lymph nodes and other organs. The mean survival time was 34 ± 10 days (n = 40) after intravenous injection and 24 ± 3 days (n = 5) after intraperitoneal injection of 20 million cells. The cells recovered from leukemic animals continued to express interleukin-3 receptors and remained sensitive to the diphtheria fusion protein DT388IL3. Further, these granulocytic sarcoma-derived cells grew again in irradiated SCID mice (n = 10). The cytogenetic abnormalities observed prior to inoculation in mice were stably present after in vivo passage. Similar to the results with v-Src transfected TF-1 cells, in vivo leukemic growth was observed with TF-1 cells transfected with the human granulocyte–macrophage colony-stimulating factor gene (n = 5) and with TF-1 cells recovered from subcutaneous tumors in nude mice (n = 5). In contrast, TF-1 cells expressing v-Ha-Ras (n = 5), BCR-ABL (n = 5), or activated Raf-1 (n = 44) did not grow in irradiated SCID mice. This is a unique, reproducible model for in vivo growth of a differentiated human acute myeloid leukemia and may be useful in the assessment of anti-leukemic therapeutics which have human-specific molecular targets such as the interleukin-3 receptor.

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Acknowledgements

This work was supported in part by the Leukemia and Lymphoma Society Grant No. 6114–99 (AEF), NIH CA76178 (AEF), NIH CA51025 (JAM) and the American Cancer Society Grant No. IRG-93–035–6 (GLK). The authors acknowledge the gift of SC-65461 and SC-50431 IL3 receptor agonist proteins from Dr Barbara Klein and Pharmacia, Inc. We thank Dr Douglas Case for input on statistical analyses.

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Authors and Affiliations

  1. Department of Cancer Biology, Pediatrics and Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    M Kiser, J Ramage, RL Alexander, GL Kucera, M Pettenati, MC Willingham, MS Miller & AE Frankel

  2. Department of Microbiology, Brody School of Medicine at East Carolina University, Greenville, NC, USA

    JA McCubrey, LS Steelman & JG Shelton

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  1. M Kiser
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Kiser, M., McCubrey, J., Steelman, L. et al. Oncogene-dependent engraftment of human myeloid leukemia cells in immunosuppressed mice. Leukemia 15, 814–818 (2001). https://doi.org/10.1038/sj.leu.2402084

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