Qualitative and quantitative characterization of Fas (APO-1/CD95) on leukemic cells derived from patients with B-cell neoplasms

Expression density and function of Fas (APO-1/CD95) on malignant B-cells, a n antigen thought responsible for abnormal tumor biology, remains to be ful ly understood. Fifty-five cases with B-cell neoplasms of acute lymphoblasti c leukemia (ALL), chronic lymphocytic leukemia (CLL), harry cell leukemia ( HCL), B-cell malignant lymphoma (ML), and myeloma (MM) were studied for qua litative and quantitative expression and function of Fas using flow cytomet ry and annexin-V staining methods. Fas expression was flow cytometrically u nimodal with heterogeneous density and showed quantitatively characteristic features among different diseases; weak in ALL, faint in CLL, moderate in HCL, and strong in ML, respectively. Not only full-length but also alternat ively spliced truncated mRNAs were detected even in leukemic B-cells with q ualitatively faint or negative Fas, and then band density of the former tra nscripts by RT-PCR was correlated to the Fas protein expression level. Shor t-term culture of freshly isolated cells gave rise to increases of Fas dens ity and susceptibility for apoptosis, suggesting that the mRNA and inducibl e Fas are functional at least in vitro. These results show that Fas is a bi ological marker for characterizing B-cell neoplasms reflecting various stag es of B-cell ontogeny and may have clinical utility as a therapeutic strate gy. (C) 1999 Elsevier Science Ltd. All rights reserved.