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Efficient and Rapid Induction of a Chronic Myelogenous Leukemia-Like Myeloproliferative Disease in Mice Receiving P210 bcr/abl-Transduced Bone Marrow

Pear, Warren S. and Miller, Juli P. and Xu, Lanwei and Pui, John C. and Soffer, Benny and Quackenbush, Robert C. and Pendergast, Ann Marie and Bronson, Roderick and Aster, Jon C. and Scott, Martin L. and Baltimore, David (1998) Efficient and Rapid Induction of a Chronic Myelogenous Leukemia-Like Myeloproliferative Disease in Mice Receiving P210 bcr/abl-Transduced Bone Marrow. Blood, 92 (10). pp. 3780-3792. ISSN 0006-4971. doi:10.1182/blood.V92.10.3780.

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Expression of the 210-kD bcr/abl fusion oncoprotein can cause a chronic myelogenous leukemia (CML)-like disease in mice receiving bone marrow cells transduced by bcr/abl-encoding retroviruses. However, previous methods failed to yield this disease at a frequency sufficient enough to allow for its use in the study of CML pathogenesis. To overcome this limitation, we have developed an efficient and reproducible method for inducing a CML-like disease in mice receiving P210 bcr/abl-transduced bone marrow cells. All mice receiving P210 bcr/abl-transduced bone marrow cells succumb to a myeloproliferative disease between 3 and 5 weeks after bone marrow transplantation. The myeloproliferative disease recapitulates many of the hallmarks of human CML and is characterized by high white blood cell counts and extensive extramedullary hematopoiesis in the spleen, liver, bone marrow, and lungs. Use of a retroviral vector coexpressing P210 bcr/abl and green fluorescent protein shows that the vast majority of bcr/abl-expressing cells are myeloid. Analysis of the proviral integration pattern shows that, in some mice, the myeloproliferative disease is clonal. In multiple mice, the CML-like disease has been transplantable, inducing a similar myeloproliferative syndrome within 1 month of transfer to sublethally irradiated syngeneic recipients. The disease in many of these mice has progressed to the development of acute lymphoma/leukemia resembling blast crisis. These results demonstrate that murine CML recapitulates important features of human CML. As such, it should be an excellent model for addressing specific issues relating to the pathogenesis and treatment of this disease.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1998 by The American Society of Hematology. Supported by National Institutes of Health Grants No. RO1CA61033 (A.M.P.), R29CA66849 (J.C.A.), and RO1CA51462 (D.B.); Special Fellowship and Scholar Awards from the Leukemia Society of America (W.S.P. and A.M.P.); Penn/Hughes Award in Developmental Biology (W.S.P.); Mary L. Smith Charitable Trust (W.S.P.); Four Schools Physician-Scientist Program sponsored by the Lucille P. Markey Charitable Trust (R.C.Q.); and the Whitehead Scholar (A.M.P.). The authors thank the following individuals: Dr J. Jacob and Dr R. Hawley for providing useful reagents; Dr R. Ren for sharing results before publication; and Dr M. Bental-Roof for critical reading of the manuscript. We thank Amgen for providing SCF. We thank the members of the University of Pennsylvania John Morgan (IHGT) and MIT mouse facilities. The flow cytometry studies were performed in the University of Pennsylvania Cancer Center Flow Cytometry and Cell Sorting Shared Resource (supported in part by the Lucille B. Markey Trust and National Cancer Institute Grant No. CA16520). The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. section 1734 solely to indicate this fact.
Funding AgencyGrant Number
Lucille B. Markey Charitable TrustUNSPECIFIED
Leukemia Society of AmericaUNSPECIFIED
Penn/Hughes Award in Developmental BiologyUNSPECIFIED
Mary L. Smith Charitable TrustUNSPECIFIED
Whitehead Institute for Biomedical ResearchUNSPECIFIED
National Cancer InstituteUNSPECIFIED
Issue or Number:10
Record Number:CaltechAUTHORS:20120111-132505555
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28749
Deposited By: Tony Diaz
Deposited On:11 Jan 2012 23:11
Last Modified:09 Nov 2021 17:00

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