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Blood, 5 March 2009, Vol. 113, No. 10, pp. 2245-2255. Prepublished online as a Blood First Edition Paper on November 6, 2008; DOI 10.1182/blood-2008-03-144071. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-03-144071v1 113/10/2245    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 Rezvani, K. Articles by Barrett, A. J. Search for Related Content PubMed PubMed Citation Articles by Rezvani, K. Articles by Barrett, A. J. Related Collections Immunobiology Myeloid Neoplasia Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 Katayoun Rezvani1,2, Agnes S. M. Yong2,*, Abdul Tawab3,*, Behnam Jafarpour2, Rhoda Eniafe2, Stephan Mielke2,4, Bipin N. Savani2,5, Keyvan Keyvanfar2, Yixin Li3, Roger Kurlander3, and A. John Barrett2 1 Department of Hematology, Imperial College, Hammersmith Campus, London, United Kingdom; 2 Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, Blood Institute and 3 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD; 4 Division of Hematology and Oncology, Department of Internal Medicine II, Würzburg University Medical Center, Würzburg, Germany; and 5 Department of Medicine, Vanderbilt University, Nashville, TN Preferentially expressed antigen of melanoma (PRAME) is aberrantly expressed in hematologic malignancies and may be a useful target for immunotherapy in leukemia. To determine whether PRAME is naturally immunogenic, we studied CD8+ T-cell responses to 4 HLA-A*0201–restricted PRAME-derived epitopes (PRA100, PRA142, PRA300, PRA425) in HLA-A*0201-positive patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and healthy donors. CD8+ T cells recognizing PRAME peptides could be detected ex vivo in 4 of 10 ALL, 6 of 10 AML, 3 of 10 CML patients, and 3 of 10 donors by HLA-A2 tetramer analysis and flow cytometry for intracellular interferon-. The frequency of PRAME-specific CD8+ T cells was greater in patients with AML, CML, and ALL than healthy controls. All peptides were immunogenic in patients, while responses were only detected to PRA300 in donors. High PRAME expression in patient peripheral blood mononuclear cells was associated with responses to greater than or equal to 2 PRAME epitopes compared with low PRAME expression levels (4/7 vs 0/23, P = .001), suggesting a PRAME-driven T-cell response. PRAME-specific T cells were readily expanded in short-term cultures in donors and patients. These results provide evidence for spontaneous T cell reactivity against multiple epitopes of PRAME in ALL, AML, and CML. The potential for developing PRAME as a target for immunotherapy in leukemia deserves further exploration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. G. Oehler, K. A. Guthrie, C. L. Cummings, K. Sabo, B. L. Wood, T. Gooley, T. Yang, M. T. Epping, Y. Shou, E. Pogosova-Agadjanyan, et al. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells Blood, October 8, 2009; 114(15): 3299 - 3308. [Abstract] [Full Text] [PDF]

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