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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2008 Accepted October 15, 2008 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 Rezvani*, Agnes S.M. Yong, Abdul Tawab, Behnam Jafarpour, Rhoda Eniafe, Stephan Mielke, Bipin N Savani, Keyvan Keyvanfar, Yixin Li, Roger Kurlander, and A John Barrett Department of Hematology, Imperial College London, London, United Kingdom Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung & Blood Institute, National Institutes of Health, Bethesda, MD, United States Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States Division of Hematology and Oncology, Department of Internal Medicine II, Wuerzburg University Medical Center, Wuerzburg, Germany Department of Medicine, Vanderbilt University, Nashville, TN, United States * Corresponding author; email: k.rezvani{at}imperial.ac.uk. PRAME (Preferentially expressed antigen of melanoma) is aberrantly expressed in hematological 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 four 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 4/10 ALL, 6/10 AML, 3/10 CML patients and 3/10 donors by HLA-A2 tetramer analysis and flow cytometry for intracellular interferon-gamma. 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, whilst responses were only detected to PRA300 in donors. High PRAME expression in patient peripheral blood mononuclear cells was associated with responses to 2 PRAME epitopes compared to low PRAME expression levels (4/7 vs. 0/23, P = 0.001), 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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