1. ¹Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya, Japan
2. ²Department of Pathology, Japanese Red Cross Nagoya 1st Hospital, Michishita-cho, Nakamura-ku, Nagoya, Japan
3. ³The Sakaguchi Laboratory of Developmental Biology, Department of Cell Differentiation, Keio University School of Medicine, Shinano-machi, Shinjuku-ku, Tokyo, Japan
4. ⁴Central Institute for Experimental Animals, Nogawa, Miyamae-ku, Kawasaki, Japan
5. ⁵Department of Infectious Diseases, Nagoya University Hospital, Tsurumai-cho, Showa-ku, Nagoya, Japan

Correspondence: Dr T Naoe, Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: tnaoe@med.nagoya-u.ac.jp

Received 8 March 2006; Revised 25 August 2006; Accepted 29 August 2006; Published online 12 October 2006.

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--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.