mRNA expression of variant Fas molecules in acute leukemia cells

Fas (Apo-1/CD95) is a cell membrane receptor involved in apoptotic cell dea th. Soluble variant forms (sFas) lacking the transmembrane domain due to al ternative splicing have been identified, Up-regulation of sFas expression i s reportedly implicated in prereceptorial blockage of Fas-induced apoptosis in a dose-dependent manner. We examined mRNA expression of Fas and sFas in fresh leukemia cells, All leukemia cells expressed both mRNAs of full-leng th Fas (FasFull) and sFas with deletion of exon6 (FasDel6). The ratio of Fa sFull/FasDel6 mRNA expression was not always correlated with Fas-mediated g rowth inhibition, interestingly, in a 6-year-old boy with acute myelogenous leukemia, blast cells obtained at onset and at the time of bone marrow rel apses expressed distinct amounts of FasDel6 mRNA, Furthermore, the level of FasDel6 expression appeared to be correlated with Fas-resistance in leukem ia blasts. In addition, sFas protein levels were elevated in patients' sera at onset with subsequent return to normal levels after complete remission. These results indicated that sFas could be synthesized and released by leu kemia blasts and suggested that up-regulation of Fas variant transcript mig ht render leukemia blasts resistant to Fas-mediated growth inhibition in ce rtain cases. (C) 1999 Wiley-Liss, Inc.