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 ex pressed in several human malignancies, and a role in the suppression of ant itumor immune responses has been suggested. We evaluated Fast expression in leukemia and normal hematopoietic cells. By Western blotting, all acute le ukemic cell lines (n = 9) and primary samples of acute leukemic marrow (n = 4) revealed high levels of Fast. In contrast, much weaker signals were obs erved in samples of normal marrow (n = 5) and either weak or intermediate e xpression was seen in chronic myeloid leukemia (CML) in chronic phase (n = 7), Additional leukemic samples were examined hg immunohistochemistry, Stai ning for Fast was negative in 7 of 9 cases of chronic-phase CML, whereas al l 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 nu cleated cells. FasL(+) leukemic cell lines did not trigger Fas-mediated apo ptosis in either Jurkat cells or activated human T lymphocytes, possibly re lated to the intracellular location of the ligand, Western analysis of norm al marrow subpopulations revealed that most Fast in marrow mononuclear cell s mas expressed by CD7(+) lymphocytes, Fast also was strongly expressed in CD34(+) hematopoietic progenitor cells from both normal and chronic-phase C ML marrow, suggesting a correlation with primitive maturation stage. In sum mary, high levels of Fast expression were associated with aggressive biolog ic behavior in leukemia, including transformation of CML to blast crisis. T his could potentially represent a response to loss of proapoptotic Fas sign aling, which is known to occur in acute leukemic blasts. (C) 1999 Internati onal Society for Experimental Hematology. Published by Elsevier Science Inc .