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From www.bloodjournal.org by guest on August 9, 2017. For personal use only. 1123 CORRESPONDENCE IS0 - Control 1- - MDS l40 120 m o 80 W 40 20 0 Fluorescence Intensity Fig 1. Fas expression in marrow mononuclear cells of a normal individual and a patient with MDS. Phycoerytherin-conjugatedmurine anti-human Far lgGl (PharMingen, San Diego, CA) was used to identify Far expression on bone marrow cells by flow cytometry. Data are representativeof findingsin four RA patients; in one patient, only a minimal increase in Fas expressionwas observed. stained for Fas than did control samples. This was particularly true for CD34+ cells (78% 2 18% for MDS, v 33% 2 11% for normal cells) as determined by double staining. If apoptosis is mediated via Fas, interactions with an agonistic ligand must occur. Indeed, there was a significant increase in FasLigand expression on marrow cells from MDS patients (37.6% 2 12.3%) compared with normal individuals (21.1% % 7.4%; n = 8) (Fig 2). The implications of our findings are crucial if interactions of Fas and Fas-Ligand are responsible for initiating apoptosis. Particularly with cell membrane-associated Fas-Ligand, apoptosis might be expected to occur in Fas-positive "clusters" of cells (as observed by Bogdanovic et al)4 adjacent to other cells expressing Fas-Ligand. Our findings in a small number of patients further complement the proposed model that Fas and Fas-Ligand are involved in the inhibition of normal hematopoiesis in patients with MDS. The event responsible for the development of MDS is generally not known. It is possible that the release of regulators such as TNF-a, TGF-P, interferon-y, or others yet to be determined results in upregulation not only of Fas, but also of Fas-Ligand. Alternatively, MDS cells, in the process of their evolution, may spontaneously upregulate Fas, Fas-Ligand, or both, or may show increased responsiveness to exogenous regulators thereby facilitating upregulation. Current studies are aimed at further characterizing, both phenotypically and functionally, cells that express either Fas, Fas-Ligand, or both. Geoffrey M. Gersuk Jong W. Lee Cassandra A. Beckham Jeanne Anderson H. Joachim Deeg Fluorescence Intensity Fig 2. Far-Ligand expression in marrow mononuclear cells ofa normal individual and a patient with MDS. Affinity-purified rabbit anti-human Fas-Ligand polyclonal antibody (Santa Crur Biotechnology, Santa Cruz, CA) was used to identify Fas-Ligand expressionon bone marrow cells by flow cytometry. The depicted pattern was seen in three RA patients; in two patients, only a moderate increase in Fas Ligand expressionwas observed. Fred Hutchinson Cancer Research Center University of Washington Seattle, WA REFERENCES 1. Philpot NJ, Scopes J, Marsh JCW, Gordon-Smith EC, Gibson FM: Increased apoptosis in aplastic anemia bone marrow progenitor cells: Possible pathophysiologic significance. Exp Hematol23:1642, 1995 2. Raza A, Gezer S, Mundle S, Gao X-Z, Alvi S, Borok R, Rifkin S, Iftikhar A, Shetty V, Parcharidou A, h e w J, Marcus B, Khan Z, Chaney C, Showel J, Gregory S, F'reislerH: Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. Blood 86:268, 1995 3. Hatake K, Tomizuka H, Ikeda M, Tsunoda JI, Hoshino Y, Ostsuki T, Tasahara T, Yonehara S, Miura Y: The presence of apoptosis in refractory anemia of myelodysplasia, in Abraham NG (ed): Molecular Biology of Haematopoiesis, v01 3. Andover, MD, Intercept, 1994, p 127 4. Bogdanovic AD, Jankovic GM, Colovic MD, Trpinac DP, Bumbasirevic VZ: Apoptosis inbonemarrow of myelodysplastic syndrome patients. Blood 87:3064, 1996 (letter) 5. Maciejewski JP, Selleri C, Sato T, Anderson S, Young NS: Increased expression of Fas antigen on bone marrow CD34' cells of patients with aplastic anemia. Br J Haematol 91:245, 1995 6. Maciejewski JP, Selleri C, Anderson S, Young NS: Fas antigen expression on CD34' human marrow cells is induced by interferon y and tumor necrosis factor a and potentiates cytokine-mediated hematopoietic suppression in vitro. Blood 85:3183, 1995 From www.bloodjournal.org by guest on August 9, 2017. For personal use only. 1996 88: 1123-1125 Growth of Epstein-Barr virus-associated B-lymphoproliferative disease tissue in a severe combined immunodeficient mouse [letter] SM Perera, I Johannessen, JA Thomas, LA Brooks, JN Jobe, DH Crawford, R Radley- Smith and M Phillips Updated information and services can be found at: http://www.bloodjournal.org/content/88/3/1123.citation.full.html Articles on similar topics can be found in the following Blood collections Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. 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