Engraftment of human T-cell acute lymphoblastic leukemia in immunodeficient NOD/SCID mice which have been preconditioned by injection of human cord blood

Childhood T-cell acute lymphoblastic leukemia (TALL) is one of the most com mon childhood cancers. Study of leukemia biology, as well as preclinical te sting 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 rep orted elsewhere some observations that human cord blood conditioned medium enhances leukemia colony formation in vitro and preconditioning of subletha lly irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice with cord blood mononuclear cells (MNCs) facilitates the subsequent e ngraftment of primary T-ALL cells in these mice. Here we characterize in gr eater detail this in vivo xenograft model of human leukemia in NOD/SCID mic e. Consistent with the thesis that cord blood facilitates engraftment, the engraftment of human leukemia can be shown to increase with increasing numb er of cord blood MNCs injected. In addition, we documented the expression o f chemokine receptor CXCR4 by primary T-ALL from patients and found that th e 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 tha t in this xenograft system T-ALL cells recovered from engrafted bone marrow are characterized by upregulated expression of interleukin 2 receptor gamm a chain, suggesting that cord blood preconditioning may function in part to increase T-ALL responsiveness to growth factor(s).