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Establishment of a Reproducible Model of Chronic-Phase Chronic
Myeloid Leukemia in NOD/SCID Mice Using Blood-Derived Mononuclear or
CD34+ Cells
Ian D. Lewis,
Louise A. McDiarmid,
Leanne M. Samels,
L. Bik To, and
Timothy P. Hughes
From the Leukaemia Research Laboratory, Division of Haematology,
Hanson Centre for Cancer Research, IMVS, Adelaide, SA, Australia.
An animal model of chronic myeloid leukemia (CML) will help
characterize leukemic and normal stem cells and also help evaluate experimental therapies in this disease. We have established a model of
CML in the NOD/SCID mouse. Infusion of  4 × 107
chronic-phase CML peripheral blood cells results in engraftment levels
of 1% in the bone marrow (BM) of 84% of mice. Engraftment of the
spleen was seen in 60% of mice with BM engraftment. Intraperitoneal injection of recombinant stem cell factor produced a higher level of
leukemic engraftment without increasing Philadelphia-negative engraftment. Granulocyte colony-stimulating factor and
granulocyte-macrophage colony-stimulating factor did not increase the
level of leukemic or residual normal engraftment. Assessment of
differential engraftment of normal and leukemic cells by fluorescence
in situ hybridization analysis with bcr and abl probes
showed that a median of 35% (range, 5% to 91%) of engrafted cells
present in the murine BM were leukemic. BM engraftment was multilineage
with myeloid, B-cell, and T-cell engraftment, whereas T cells were the
predominant cell type in the spleen. BM morphology showed evidence of
eosinophilia and increased megakaryocytes. We also assessed the ability
of selected CD34+ CML blood cells to engraft NOD/SCID
mice and showed engraftment with cell doses of 7 to 10 × 106 cells. CD34 cells failed to engraft at
cell doses of 1.2 to 5 × 107. CD34+ cells
produced myeloid and B-cell engraftment with high levels of
CD34+ cells detected. Thus, normal and leukemic stem
cells are present in CD34+ blood cells from CML patients
at diagnosis and lead to development of the typical features of CML in
murine BM. This model is suitable to evaluate therapy in CML.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 630-640
© 1998 by The American Society of Hematology.
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