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BCR-ABL Activity Is Critical for the Immunogenicity of Chronic Myelogenous Leukemia Cells

Department of Hematology, Oncology, Immunology, Rheumatology, and Pulmonology, University of Tübingen, Tübingen, Germany

Requests for reprints: Peter Brossart, Department of Hematology, Oncology and Immunology, University of Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. Phone: 49-7071-29-82726; Fax: 49-7071-29-5709; E-mail: peter.brossart{at}med.uni-tuebingen.de.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by excessive granulopoiesis due to the formation of the constitutively active tyrosine kinase BCR-ABL. An effective drug against CML is imatinib mesylate, a tyrosine kinase inhibitor acting on Abl kinases, c-KIT, and platelet-derived growth factor receptor. Recently, a study revealed that patients treated with imatinib showed impaired CTL responses compared with patients treated with IFN-, which might be due to a treatment-induced reduction in immunogenicity of CML cells or immunosuppressive effects. In our study, we found that inhibition of BCR-ABL leads to a down-regulation of immunogenic antigens on the CML cells in response to imatinib treatment, which results in the inhibition of CML-directed immune responses. By treating CML cells with imatinib, we could show that the resulting inhibition of BCR-ABL leads to a decreased expression of tumor antigens, including survivin, adipophilin, hTERT, WT-1, Bcl-x_L, and Bcl-2 in correlation to a decreased development of CML-specific CTLs. In contrast, this reduction in immunogenicity was not observed when a CML cell line resistant to the inhibitory effects of imatinib was used, but could be confirmed by transfection with specific small interfering RNA against BCR-ABL or imatinib treatment of primary CML cells. [Cancer Res 2007;67(11):5489–97]

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				C. I-U. Chen, H. T. Maecker, and P. P. Lee Development and dynamics of robust T-cell responses to CML under imatinib treatment Blood, June 1, 2008; 111(11): 5342 - 5349. [Abstract] [Full Text] [PDF]