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Stem Cells

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice

Leukemia volume 21, pages 136–142 (2007)Cite this article

Abstract

The cellular components of the hematopoietic stem cell niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells, which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferation and survival sites by immunohistopathology, compared with the corresponding sites for cord blood CD34+ (CBCD34+) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34+ leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5-bromo-2′-deoxyuridine labeling revealed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34+ cells showed the similar pattern of homing and proliferation to leukemia cells. After high-dose administration of cytosine-1-β-D-arabinofuranoside, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche.

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Acknowledgements

This study was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, and the Pharmaceuticals and Medical Devices Agency. We thank Ms Satomi Yamaji and Yuka Nomura for technical assistance, and Ms Manami Kira and Mari Otsuka for secretarial assistance.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, Japan

    M Ninomiya, A Abe, A Katsumi, J Xu, T Kinoshita & T Naoe

  2. Department of Pathology, Japanese Red Cross Nagoya 1st Hospital, Michishita-cho, Nakamura-ku, Nagoya, Japan

    M Ito

  3. Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, Shinano-machi, Shinjuku-ku, Tokyo, Japan

    F Arai & T Suda

  4. Central Institute for Experimental Animals, Nogawa, Miyamae-ku, Kawasaki, Japan

    M Ito

  5. Department of Infectious Diseases, Nagoya University Hospital, Tsurumai-cho, Showa-ku, Nagoya, Japan

    H Kiyoi

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  1. M Ninomiya
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Correspondence to T Naoe.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Ninomiya, M., Abe, A., Katsumi, A. et al. Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. Leukemia 21, 136–142 (2007). https://doi.org/10.1038/sj.leu.2404432

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