Fas ligand is highly expressed in acute leukemia and during the transformation of chronic myeloid leukemia to blast crisis

Fas ligand (FasL) induces apoptosis in susceptible Fas-bearing cells and is critically involved in regulating T-cell immune responses. It is highly expressed in several human malignancies, and a role in the suppression of antitumor immune responses has been suggested. We evaluated Fast expression in leukemia and normal hematopoietic cells. By Western blotting, all acute leukemic cell lines (n = 9) and primary samples of acute leukemic marrow (n = 4) revealed high levels of Fast. In contrast, much weaker signals were observed in samples of normal marrow (n = 5) and either weak or intermediate expression was seen in chronic myeloid leukemia (CML) in chronic phase (n = 7), Additional leukemic samples were examined hg immunohistochemistry, Staining for Fast was negative in 7 of 9 cases of chronic-phase CML, whereas all cases of CML in blast crisis (n = 6), acute lymphoblastic leukemia (n = 6), and acute myeloid leukemia (n = 11) stained strongly in 60 to 100% of nucleated cells. FasL(+) leukemic cell lines did not trigger Fas-mediated apoptosis in either Jurkat cells or activated human T lymphocytes, possibly related to the intracellular location of the ligand, Western analysis of normal marrow subpopulations revealed that most Fast in marrow mononuclear cells mas expressed by CD7(+) lymphocytes, Fast also was strongly expressed in CD34(+) hematopoietic progenitor cells from both normal and chronic-phase CML marrow, suggesting a correlation with primitive maturation stage. In summary, high levels of Fast expression were associated with aggressive biologic behavior in leukemia, including transformation of CML to blast crisis. This could potentially represent a response to loss of proapoptotic Fas signaling, which is known to occur in acute leukemic blasts. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.