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Blood, 1 August 2005, Vol. 106, No. 3, pp. 841-851. Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-05-2017. This Article Full Text (PDF) All Versions of this Article: 2004-05-2017v1 106/3/841    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 Sloand, E. M Articles by Young, N. S Search for Related Content PubMed PubMed Citation Articles by Sloand, E. M Articles by Young, N. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 3, 2004 Accepted March 10, 2005 Preferential suppression of trisomy 8 versus normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome Elaine M Sloand*, Lori Mainwaring, Monika Fuhrer, Shakti Ramkissoon, Antonio M Risitano, Keyvan Keyvanafar, Jun Lu, Atanu Basu, A J Barrett, and Neal S Young Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA * Corresponding author; email: sloande{at}nih.gov. Clinical observations and experimental evidence link bone marrow failure in myelodysplastic syndrome (MDS) with a T cell-dominated autoimmune process. Immunosuppressive therapy is effective in improving cytopenias in selected cases. Trisomy 8 is a frequent cytogenetic abnormality present in bone marrow cells in patients with MDS and its presence has anecdotally been associated with good response to immunotherapy. We studied 34 patients with trisomy 8 in bone marrow cells, some of whom were undergoing treatment with antithymocyte globulin (ATG). All had significant CD8+ T cell expansions of one or more TCR V subfamilies as measured by flow cytometry; expanded subfamilies showed CDR3 skewing by spectratyping. Sorted T cells of the expanded V subfamilies, but not of the remaining subfamilies, inhibited proliferation of trisomy 8 cells in short-term culture. The negative effects of V-expanded T cells were inhibited by MHC class I monoclonal antibody (mAb) and Fas antagonist and required direct cell-to-cell contact. Sixty-seven percent of de novo MDS patients with trisomy 8 as the sole karyotypic abnormality responded to ATG with durable reversal of cytopenias and restoration of transfusion-independence, with stable increase in the proportion of trisomy 8 bone marrow cells and normalization of the T cell repertoire. Increased T cells with apparent specificity for trisomy 8 cells are consistent with an autoimmune pathophysiology in trisomy 8 MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. Barrett and E. Sloand Autoimmune mechanisms in the pathophysiology of myelodysplastic syndromes and their clinical relevance Haematologica, April 1, 2009; 94(4): 449 - 451. [Full Text] [PDF] M. E.D. Chamuleau, T. M. Westers, L. van Dreunen, J. Groenland, A. Zevenbergen, C. M. Eeltink, G. J. Ossenkoppele, and A. A. van de Loosdrecht Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome Haematologica, April 1, 2009; 94(4): 496 - 506. [Abstract] [Full Text] [PDF] A. Shenoy, L. Pfannes, F. Wilhelm, M. Maniar, N. Young, and E. M Sloand Suppression of Cyclin D 1 (CD1) by on 01910.Na Is Associated with Decreased Survival or Trisomy 8 Myelodysplastic Bone Marrow: A Potential Targetted Therapy for Trisomy 8 MDS. Blood (ASH Annual Meeting Abstracts), November 16, 2008; 112(11): 1651 - 1651. [Abstract] [Full Text] S. Y. Kordasti, W. Ingram, J. Hayden, D. Darling, L. Barber, B. Afzali, G. Lombardi, M. W. Wlodarski, J. P. Maciejewski, F. Farzaneh, et al. CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS) Blood, August 1, 2007; 110(3): 847 - 850. [Abstract] [Full Text] [PDF] E. M. Sloand, L. Pfannes, G. Chen, S. Shah, E. E. Solomou, J. Barrett, and N. S. Young CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins Blood, March 15, 2007; 109(6): 2399 - 2405. [Abstract] [Full Text] [PDF] E. M. Sloand, K. Rezvani, A. Yong, D. Douek, R. Kurlander, D. Price, J. Barrett, and N. S. Young Cytotoxic CD8 T Cell Immune Responses to Wilms Tumor Protein (WT-1) Characterizes Immunosuppression-Responsive Myelodysplasia (MDS). Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 849 - 849. [Abstract] [Full Text] [PDF] N. S. Young, R. T. Calado, and P. Scheinberg Current concepts in the pathophysiology and treatment of aplastic anemia Blood, October 15, 2006; 108(8): 2509 - 2519. [Abstract] [Full Text] [PDF] K. Ogata, Y. Kishikawa, C. Satoh, H. Tamura, K. Dan, and A. Hayashi Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes Blood, August 1, 2006; 108(3): 1037 - 1044. [Abstract] [Full Text] [PDF] T. Braun, G. Carvalho, A. Coquelle, M.-C. Vozenin, P. Lepelley, F. Hirsch, J.-J. Kiladjian, V. Ribrag, P. Fenaux, and G. Kroemer NF-{kappa}B constitutes a potential therapeutic target in high-risk myelodysplastic syndrome Blood, February 1, 2006; 107(3): 1156 - 1165. [Abstract] [Full Text] [PDF] N. S. Young Pathophysiologic Mechanisms in Acquired Aplastic Anemia Hematology, January 1, 2006; 2006(1): 72 - 77. [Abstract] [Full Text] [PDF]

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