RESISTANCE TO APOPTOTIC CELL-DEATH IN A DRUG-RESISTANT T-CELL LEUKEMIA-CELL LINE

In this study, we investigated the responses of the T cell leukaemia c ell line, CCRF-CEM, and a vincristine-resistant subline, CEM/VCR R, to the induction of cell death by serum withdrawal. This treatment was u sed to overcome any contribution of P-glycoprotein-mediated drug resis tance to the responses of the CEM/VCR R cells. Following serum withdra wal both cell lines exhibited typical apoptotic responses including mo rphological changes and nucleosomal cleavage of the DNA. However, usin g several different assays for cell death the CEM/VCR R cell line was shown to undergo apoptosis at a slower rate than the parental CCRF-CEM cell line. Expression of c-Myc, Bcl-2 and p53 was found to be similar in both cell lines, discounting involvement of these proteins in the observed difference in apoptotic response. Given our previous finding that reorganisation of tubulin is involved in apoptosis, we examined t he expression of alpha-, beta- and acetylated alpha-tubulin in the par ental and resistant lines, The CEM/VCR R cell line had altered tubulin expression when compared to that of the CCRF-CEM line. Transnuclear m icrotubule networks were observed in log phase CEM/VCR R cells. In add ition, increased expression of the acetylated form of the cu-tubulin i sotype suggested that a more stable microtubule network was present in the CEM/VCR R cells. These findings imply that the drug-resistance ph enotype in the CEM/VCR R cells may involve the suppression of apoptosi s, and that the development of an altered microtubule network may cont ribute to this suppression.