Preconditioning with fetal cord blood facilitates engraftment of primary childhood T-cell acute lymphoblastic leukemia in immunodeficient mice

Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the most co mmon childhood cancers. It is reported that preconditioning sublethally irr adiated immunodeficient NOD/SCID (nonobese diabetic/X-linked severe combine d immunodeficient) mice with human cord blood mononuclear cells facilitates the engraftment, expansion, and dissemination in these mice of primary T-A LL cells obtained from patients at the time of diagnosis. Cells recovered f rom mouse bone marrow or spleen resembled the original leukemia cells from patients with respect to surface lineage markers and T-cell receptor V beta gene rearrangements. Moreover, the pattern of leukemia dissemination in mo use tissues, resulting in universally fatal leukemia, is reminiscent of the human clinical disease. In addition, the fidelity of the model to the huma n disease is documented with regard to the presence of morphologically iden tifiable human leukemia cells in mouse bone marrow and blood and the mainte nance of leukemia-initiating capacity within the leukemia-engrafted mouse. Therefore, several lines of independent approaches are used to suggest that the engrafted cells are of human leukemia origin and are not derived from cord blood. The in vivo model described here should enable the study of the growth properties of primary T-ALL cells obtained from patients and should prove useful in evaluating the potential efficacy of therapeutic strategie s directed toward T-ALL. (Blood. 2001;97:3218-3225) (C) 2001 by The America n Society of Hematology.