FUNCTIONAL EXPRESSION OF FAS (CD95) IN ACUTE MYELOID-LEUKEMIA CELLS IN THE CONTEXT OF CD34 AND CD38 EXPRESSION - POSSIBLE CORRELATION WITH SENSITIVITY TO CHEMOTHERAPY

Clinical studies of bone marrow transplantation (BMT) suggest that the immune system contributes to the eradication of acute myeloid leukemi a (AML). A recent study also showed that the Fas (CD95/AP01) mediates apoptotic signal from cytotoxic T lymphocytes. Sixty-four patients wit h AML were studied for the expression of Fas in the context of CD34 an d CD38 coexpression. The clinical relevance of Fas expression and func tion on AML was also investigated. Fas was expressed on 2% to 98% of A ML cells (2% to 20% in 11 patients, 20% to 50% in 20 patients, 50% to 80% in 24 patients, and 80% to 98% in nine patients). Only 44.4% of pa tients with AML M1 (French-American-British [FAB] classification) were Fas(+) (greater than or equal to 20% of leukemia cells expressed Fas) , whereas 89.1% of patients with AML M2, M3, M4, M5 were Fas(+) (P < . 01). Among 43 CD34(+) patients (greater than or equal to 20% leukemia cells were CD34(+)), 34 were Fas(+), and 19 of 21 CD34(-) patients wer e Fas(+) (P = NS). Thirteen cases were studied for their expression of Fas in the context of CD34 and CD38 using three-color analysis. Fas i s expressed at a high level in the gated CD34(+)CD38(+/-) and CD34(+)C D38(+) population. In 10 AML samples, Fas was expressed at a higher le vel in CD34(+)/CD38(+) population than in CD34(+)/CD38(+/-) or CD34(-) cell populations. Fas-induced apoptosis by anti-fas monoclonal antibo dy (MoAb) was determined by morphologic features and colorimetric DNA fragmentation assay. Induction of apoptosis was found in 14 of 24 case s. However, no statistically significant correlation was observed betw een Fas expression and induction of apoptosis. Leukemia colony-forming unit assays suggested that in some cases, Fas-induced apoptosis occur red in the clonogenic cell populations. Parameters such as laboratory and clinical data at initial diagnosis were correlated with Fas expres sion and only response to initial induction chemotherapy showed signif icant correlation with Fas expression (P < .05). We conclude that the majority of AML cells exhibit variable expression of Fas, and apoptosi s could be induced by anti-fas MoAb in some cases. Our results suggest the Fas-mediated apoptosis may be clinically relevant, whereas the is sue of clonogenic leukemia cells and Fas expression needs further stud ies. (C) 1997 by The American Society of Hematology.