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

M. Ninomiya, A. Abe, A. Katsumi, J. Xu, M. Ito, F. Arai, T. Suda, M. Ito, H. Kiyoi, T. Kinoshita, T. Naoe

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalLeukemia
Volume21
Issue number1
DOIs
Publication statusPublished - 2007 Jan

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Leukemia
Survival
Fetal Blood
Blood Cells
Stem Cell Niche
Heterologous Transplantation
Epiphyses
Cytosine
Hematopoiesis
Bromodeoxyuridine
Hematopoietic Stem Cells
Osteoblasts
Bone Marrow Cells
Endothelium
Blood Vessels
Catalytic Domain
Cell Proliferation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Ninomiya, M., Abe, A., Katsumi, A., Xu, J., Ito, M., Arai, F., ... Naoe, T. (2007). Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. Leukemia, 21(1), 136-142. https://doi.org/10.1038/sj.leu.2404432

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. / Ninomiya, M.; Abe, A.; Katsumi, A.; Xu, J.; Ito, M.; Arai, F.; Suda, T.; Ito, M.; Kiyoi, H.; Kinoshita, T.; Naoe, T.

In: Leukemia, Vol. 21, No. 1, 01.2007, p. 136-142.

Research output: Contribution to journalArticle

Ninomiya, M, Abe, A, Katsumi, A, Xu, J, Ito, M, Arai, F, Suda, T, Ito, M, Kiyoi, H, Kinoshita, T & Naoe, T 2007, 'Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice', Leukemia, vol. 21, no. 1, pp. 136-142. https://doi.org/10.1038/sj.leu.2404432
Ninomiya, M. ; Abe, A. ; Katsumi, A. ; Xu, J. ; Ito, M. ; Arai, F. ; Suda, T. ; Ito, M. ; Kiyoi, H. ; Kinoshita, T. ; Naoe, T. / Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. In: Leukemia. 2007 ; Vol. 21, No. 1. pp. 136-142.
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