Constitutive expression levels of CD95 and Bcl-2 as well as CD95 function and spontaneous apoptosis in vitro do not predict the response to inductionchemotherapy and relapse rate in childhood acute lymphoblastic leukaemia

CD95 (Fas/APO-1) expression and function and Bcl-2 expression, as well as s pontaneous apoptosis in vitro, hare been shown to be predictive markers for the in vivo response to chemotherapy in acute myeloid leukaemia (AML). To determine the clinical significance of apoptosis-regulating factors in acut e lymphoblastic leukaemia (ALL), we investigated cell samples of children w ith ALL who had been included in the German ALL Berlin-Frankfurt-Munster (B FM) study using flow cytometry for constitutive expression levels of CD95 ( n = 110) and Bcl-2 (n = 110). Furthermore, we determined the extent of spon taneous apoptosis in vitro (n = 102) and susceptibility to anti-CD95-induce d apoptosis (CD95-sensitivity) (n = 97). We correlated these findings with the functional activity of the multidrug resistance (MDR)-associated P-glyc oprotein (P-gp), as detected by the rhodamine123 efflux test, immunophenoty pe, cytogenetics and clinical data of the patients examined. Good responder s to initial prednisone therapy ('prednisone response') revealed significan tly higher Bcl-2 expression levels [5.4 +/- 3.4 relative fluorescence inten sity (RFI), n = 68] than poor responders (3.7 +/- 2.6 RFI, n = 42; P = 0.00 2). There was no significant correlation between the other in investigated parameters and prednisone response. Moreover, neither the CD95 and Bcl-2 ex pression levels nor the extent of spontaneous apoptosis in vitro, CD95 sens itivity or P-gp function were correlated with the response to induction che motherapy or relapse rate, either for B-cell precursor ALL or T-cell ALL. N o consistent pattern of change in CD95 (n = 10) and Bcl-2 expression (n = 9 ) was noted in cases studied at both initial diagnosis and relapse. In conc lusion, our findings underline the different cell biological features of pr imary AML and ALL cells.