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Prepublished online as a Blood First Edition Paper on February 20, 2003; DOI 10.1182/blood-2002-10-3059. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3059v1 101/12/5010    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wolff, N. C. Articles by Ilaria, R. L. Search for Related Content PubMed PubMed Citation Articles by Wolff, N. C. Articles by Ilaria, R. L., Jr Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 5010-5013 NEOPLASIA Brief report The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate for Bcr/Abl-induced leukemia Nicholas C. Wolff, James A. Richardson, Merrill Egorin, and Robert L. Ilaria, Jr From the Division of Hematology/Oncology, Department of Medicine, Simmons Cancer Center and the Hamon Center for Therapeutic Oncology Research, and the Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX; and the Departments of Medicine and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh, PA. The chronic myelogenous leukemia (CML)–like myeloproliferative disorder observed in the BCR/ABL murine bone marrow transduction and transplantation model shares several features with the human disease, including a high response rate to the tyrosine kinase inhibitor imatinib mesylate (STI571). To study the impact of chronic imatinib mesylate treatment on the CML-like illness, mice were maintained on therapeutic doses of this drug and serially monitored. Unexpectedly, despite excellent systemic control of the CML-like illness, many of the mice developed progressive neurologic deficits after 2 to 4 months of imatinib mesylate therapy because of central nervous system (CNS) leukemia. Analysis of imatinib mesylate cerebral spinal fluid concentrations revealed levels 155- fold lower than in plasma. Thus, in the mouse, the limited ability of imatinib mesylate to cross the blood-brain barrier allowed the CNS to become a sanctuary for Bcr/Abl-induced leukemia. This model will be a useful tool for the future study of novel anti-CML drugs and in better defining the mechanisms for limited imatinib mesylate penetration into the CNS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Larmonier, N. Janikashvili, C. J. LaCasse, C. B. Larmonier, J. Cantrell, E. Situ, T. Lundeen, B. Bonnotte, and E. Katsanis Imatinib Mesylate Inhibits CD4+CD25+ Regulatory T Cell Activity and Enhances Active Immunotherapy against BCR-ABL- Tumors J. Immunol., November 15, 2008; 181(10): 6955 - 6963. [Abstract] [Full Text] [PDF] A. R. Alvarez, A. Klein, J. Castro, G. I. Cancino, J. Amigo, M. Mosqueira, L. M. Vargas, L. F. Yevenes, F. C. Bronfman, and S. Zanlungo Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease FASEB J, October 1, 2008; 22(10): 3617 - 3627. [Abstract] [Full Text] [PDF] G. I. Cancino, E. M. 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