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Homing and progression patterns of childhood acute lymphoblastic leukemias
in severe combined immunodeficiency mice
A Cesano, R O'Connor, B Lange, J Finan, G Rovera and D Santoli
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
The aim of this study was to analyze the homing and progression patterns of
childhood acute lymphoblastic leukemias (ALL) in mice with severe combined
immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from
relapse samples of three children with T-lineage ALL spread hematogenously
and infiltrated the non-lymphoid and/or lymphoid organs with a pattern
reminiscent of the human clinical disease. These mice either died or were
killed in extremis at a mean of 9 weeks. Moreover, cell lines established
in vitro from two of these samples manifested identical homing and
progression in the SCID mouse as compared with the original patients'
cells. Thus, long-term culture of the primary leukemic T cells did not
alter their invasive potential and migration pattern. When engrafted IP,
three cell lines established from pre-B-ALL cases displayed primarily a
lymphatic spread with induction of local tumor masses and kidney/liver
nodules. Mice were killed at 11 to 13 weeks, but had not developed
imminently fatal leukemia. However, when transferred intravenously, one
pre-B ALL cell line was able to spread hematogenously and to infiltrate
both lymphoid and non-lymphoid tissues. Overall, these data demonstrate
that the SCID mouse provides an efficient and reproducible model to study
the pathogenesis of childhood ALL, and may be a suitable system for
evaluating therapy.
Volume 77,
Issue 11,
pp. 2463-2474,
06/01/1991
Copyright © 1991 by The American Society of Hematology
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