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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3218-3225
NEOPLASIA
Preconditioning with fetal cord blood facilitates engraftment of
primary childhood T-cell acute lymphoblastic leukemia in
immunodeficient mice
Deno P. Dialynas,
Mi-Jeong Lee,
Daniel P. Gold,
Li-en Shao,
Alice L. Yu,
Michael J. Borowitz, and
John Yu
From the Department of Molecular and Experimental
Medicine, The Scripps Research Institute, La Jolla; the Department of
Pediatrics, University of California at San Diego Medical Center; the
Immunology Program, Sidney Kimmel Cancer Center, San Diego, CA; and the
Department of Pathology, Johns Hopkins University, Baltimore, MD.
Childhood T-cell acute lymphoblastic leukemia (T-ALL) is one of the
most common childhood cancers. It is reported that preconditioning sublethally irradiated immunodeficient NOD/SCID (nonobese
diabetic/X-linked severe combined immunodeficient) mice with human
cord blood mononuclear cells facilitates the engraftment,
expansion, and dissemination in these mice of primary T-ALL cells
obtained from patients at the time of diagnosis. Cells recovered from
mouse bone marrow or spleen resembled the original leukemia cells from
patients with respect to surface lineage markers and T-cell receptor
V gene rearrangements. Moreover, the pattern of leukemia
dissemination in mouse tissues, resulting in universally fatal
leukemia, is reminiscent of the human clinical disease. In addition,
the fidelity of the model to the human disease is documented with
regard to the presence of morphologically identifiable human leukemia
cells in mouse bone marrow and blood and the maintenance 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 strategies directed toward T-ALL.
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