Michael W. Deininger

The susceptibility of Philadelphia chromosome positive cells to FAS‐mediated apoptosis is not linked to the tyrosine kinase activity of BCR‐ABL

We investigated whether inhibition of the BCR‐ABL tyrosine kinase by the CGP57418B compound would render chronic myeloid leukaemia (CML) cells susceptible to Fas (CD95, Apo‐1)‐mediated cell death. Only two (AR230 and SD1) out of 10 BCR‐ABL positive cell lines were found to express the CD95 protein. No change in Fas expression was observed in any of the 10 cell lines after 48 h exposure to CGP57418B. AR230 cells were resistant and SD1 cells were partially resistant to Fas‐mediated apoptosis induced by ligation of the Fas receptor to an anti‐Fas IgM antibody. Pre‐incubation with 1 μM CGP57418B did not change the susceptibility of these cell lines to Fas‐mediated cell death. Similar results were observed in experiments with CD34+ cells from CML patients and from normal individuals. The data suggest that, in contrast to some cytotoxic drugs, the CGP57148B tyrosine kinase inhibitor utilizes a pathway other than the CD95 system in order to induce apoptosis in CML cells.