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Stem Cells, Vol. 19, No. 5, 443-452, September 2001
© 2001 AlphaMed Press

Engraftment of Human T-Cell Acute Lymphoblastic Leukemia in Immunodeficient NOD/SCID Mice Which Have Been Preconditioned by Injection of Human Cord Blood

Deno P. Dialynasa, Li-en Shaoa, Glenn F. Billmanb, John Yua,c

a Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California;
b Department of Pathology, Children's Hospital, San Diego, California;
c Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA

Key Words. Leukemia engraftment • Immunodeficient mouse • Chemokine receptor CXCR4 • IL-2R {gamma} chain

John Yu, M.D., Ph.D., Department of Molecular and Experimental Medicine, MEM 265, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. Telephone: 858-784-7924; Fax: 858-784-7977; e-mail: JohnYu{at}scripps.edu

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most common childhood cancers. Study of leukemia biology, as well as preclinical testing of potential therapeutic regimens directed at T-ALL, has been impeded by the lack of an efficient in vivo model of primary leukemia. We have reported elsewhere some observations that human cord blood conditioned medium enhances leukemia colony formation in vitro and preconditioning of sublethally irradiated nonobese diabetic/ severe combined immunodeficient (NOD/SCID) mice with cord blood mononuclear cells (MNCs) facilitates the subsequent engraftment of primary T-ALL cells in these mice. Here we characterize in greater detail this in vivo xenograft model of human leukemia in NOD/SCID mice. Consistent with the thesis that cord blood facilitates engraftment, the engraftment of human leukemia can be shown to increase with increasing number of cord blood MNCs injected. In addition, we documented the expression of chemokine receptor CXCR4 by primary T-ALL from patients and found that the presence of these receptors did not result in the transmigration of T-ALL cells induced by stromal cell-derived factor-1{alpha}. Finally, we show that in this xenograft system T-ALL cells recovered from engrafted bone marrow are characterized by upregulated expression of interleukin 2 receptor {gamma} chain, suggesting that cord blood preconditioning may function in part to increase T-ALL responsiveness to growth factor(s).




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