Bcr-Abl Activity Is Critical For The Immunogenicity Of Chronic Myelogenous Leukemia Cells.

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by excessive granulopoiesis due to the forma- tion 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-A, 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 ima- tinib, 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-xL, and Bcl-2 in corre- lation 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)