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Propagation of human blastic myeloid leukemias in the SCID mouse
CL Sawyers, ML Gishizky, S Quan, DW Golde and ON Witte
Department of Medicine, University of California-Los Angeles 90024.
Existing in vitro culture technology does not permit the routine
propagation of most human myeloid leukemias. Previous work has shown the
usefulness of mice with severe combined immunodeficiency (SCID) for the
growth of human lymphoblastic leukemia. We show here that human myeloid
cell lines and bone marrow samples from patients with acute myeloid
leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow
in SCID mice. Human AML or CML cell lines (three of three lines tested)
grew in the bone marrow and peripheral blood of the mice after intravenous
(IV) inoculation in a pattern closely resembling human AML. To define the
best conditions for the growth of primary human myeloid leukemia cells,
samples were transplanted into mice at several alternative sites. Using
flow cytometry and Southern analysis, mice were analyzed at defined
intervals up to 36 weeks after transplantation for the presence of human
cells in various tissues. For four of four patients with AML and two of two
patients with blast crisis of CML, myeloblasts grew locally at the site of
implantation and were detected in the murine hematopoietic tissues. In
contrast, marrow implants from patients in the chronic phase of CML (six
patients) showed infrequent and limited myeloid growth in the mice. These
findings demonstrate that the SCID mouse is a reproducible system for the
propagation of blastic human myeloid leukemias. The differential growth of
early- versus late-phase CML suggests that the SCID mouse may be a useful
assay for identifying biologically aggressive leukemias early in their
clinical presentation.
Volume 79,
Issue 8,
pp. 2089-2098,
04/15/1992
Copyright © 1992 by The American Society of Hematology
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