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Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1390-1396
The Kinetics and Extent of Engraftment of Chronic Myelogenous
Leukemia Cells in Non-Obese Diabetic/Severe Combined
Immunodeficiency Mice Reflect the Phase of the Donor's
Disease: An In Vivo Model of Chronic Myelogenous Leukemia Biology
Francesco Dazzi,
Debora Capelli,
Robert Hasserjian,
Finbarr Cotter,
Margherita Corbo,
Alessandro Poletti,
Wimol Chinswangwatanakul,
John M. Goldman, and
Myrtle Y. Gordon
From the Departments of Haematology and Histopathology, Imperial
College School of Medicine at Hammersmith Hospital, London; LRF Centre
for Childhood Leukaemia, Institute of Child Health, London, UK; and the
Department of Pathology, Padua University, Padua, Italy.
In vitro studies have provided little consensus on the kinetic
abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may
therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOD/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry
using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene.
One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site.
Similar short-term kinetics were observed using
51Cr-labeled cells. The first signs of engraftment for
BV173, AP, and BP cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine
marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP,
38.5% (range, 18 to 79) for BP, and 54% (range, 31 to 69) for
BV173. CP cells progressively infiltrated BM (21%) and
spleen (6%) by 18 to 20 weeks; no animals injected with the cell line
or BP cells survived beyond 12 weeks. The rate of increase in human
cell numbers was higher for BP (7.3%/week) as compared
with CP (0.9%/week) and AP (0.5%/week). FISH analysis with BCR and
ABL probes showed that some of the human cells engrafting after
injection of CP cells lacked a BCR-ABL gene and were presumably normal.
We conclude that CML cells proliferate in NOD/SCID mice with kinetics
that recapitulate the phase of the donor's disease, thus providing an
in vivo model of CML biology.
© 1998 by The American Society of Hematology.
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