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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 (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 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 Social Bookmarking                   What's this? Submitted October 8, 2002 Accepted February 5, 2003 The CNS is a sanctuary for leukemic cells in mice receiving imatinib mesylate (STI571) for Bcr/Abl-induced leukemia Nicholas C Wolff, James A Richardson, Merrill Egorin, and Robert L Ilaria* Division of Hematology/Oncology, Department of Medicine, Simmons Cancer Center and the Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA Departments of Medicine and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburg, PA, USA * Corresponding author; email: rilari{at}mednet.swmed.edu. 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 STI571 (imatinib mesylate). To study the impact of chronic STI571 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 neurological deficits after 2-4 months of STI571 therapy because of CNS leukemia. Analysis of STI571 CSF concentrations revealed levels 155-fold lower than in plasma. Thus, in the mouse, the limited ability of STI571 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 STI571 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. 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