CORRESPONDENCE 1123 Fluorescence Intensity

Fig 1. Fas expression in marrow mononuclear cells of a normal individual and a patient with MDS. Phycoerytherin-conjugated mu-rine anti-human Far lgGl (PharMingen, San Diego, CA) was used to identify Far expression on bone marrow cells by flow cytometry. Data are representative of findings in four RA patients; in one patient, only a minimal increase in Fas expression was 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 Fas-Ligand 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. Par-ticularly 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 exog-enous regulators thereby facilitating upregulation. Current studies are aimed at further characterizing, both phenotypically and func-tionally, cells that express either Fas, Fas-Ligand, or both