This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grünebach, F. Articles by Brossart, P. Search for Related Content PubMed PubMed Citation Articles by Grünebach, F. Articles by Brossart, P.

BCR-ABL Is Not an Immunodominant Antigen in Chronic Myelogenous Leukemia

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

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

In the present study, we analyzed the involvement of the BCR-ABL protein in the induction of antigen-specific CTL in order to develop an immunotherapeutic approach in patients with chronic myelogenous leukemia (CML). To accomplish this, we generated dendritic cells (DC) in vitro and electroporated them with various sources of RNA harboring the chimeric bcr-abl transcript. These genetically engineered DCs were used as antigen-presenting cells for the induction of CTLs. By applying this approach, we found that the CTLs induced by DCs transfected with RNA extracted from bcr-abl–positive K-562 cells or CML blasts lysed DCs transfected with the corresponding RNA, but failed to recognize epitopes derived from the chimeric BCR-ABL fusion protein in ⁵¹Cr-release assays. In contrast, they were able to lyse autologous DCs electroporated with RNA isolated from patients with acute myeloid leukemia, indicating that antigens shared among these malignant cells are involved and recognized by these CTLs. In patients with CML in complete cytogenetic remission during IFN- treatment, we detected some reactivity of CD8⁺ T cells against BCR-ABL in IFN- ELISPOT assays, which was weaker as compared with proteinase 3 (PR3)- or prame-directed responses, suggesting that the BCR-ABL protein is less immunogenic as compared with other CML-derived antigens. (Cancer Res 2006; 66(11): 5892-900)

This article has been cited by other articles:

				K. Rezvani, A. S. M. Yong, A. Tawab, B. Jafarpour, R. Eniafe, S. Mielke, B. N. Savani, K. Keyvanfar, Y. Li, R. Kurlander, et al. Ex vivo characterization of polyclonal memory CD8+ T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia Blood, March 5, 2009; 113(10): 2245 - 2255. [Abstract] [Full Text] [PDF]

				F. Scheich, J. Duyster, C. Peschel, and H. Bernhard The immunogenicity of Bcr-Abl expressing dendritic cells is dependent on the Bcr-Abl kinase activity and dominated by Bcr-Abl regulated antigens Blood, October 1, 2007; 110(7): 2556 - 2560. [Abstract] [Full Text] [PDF]

				G. Volpe, A. Cignetti, C. Panuzzo, M. Kuka, K. Vitaggio, M. Brancaccio, G. Perrone, M. Rinaldi, G. Prato, M. Fava, et al. Alternative BCR/ABL Splice Variants in Philadelphia Chromosome-Positive Leukemias Result in Novel Tumor-Specific Fusion Proteins that May Represent Potential Targets for Immunotherapy Approaches Cancer Res., June 1, 2007; 67(11): 5300 - 5307. [Abstract] [Full Text] [PDF]

				J. Roman-Gomez, A. Jimenez-Velasco, X. Agirre, J. A. Castillejo, G. Navarro, E. San Jose-Eneriz, L. Garate, L. Cordeu, F. Cervantes, F. Prosper, et al. Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia Haematologica, February 1, 2007; 92(2): 153 - 162. [Abstract] [Full Text] [PDF]