Summary. To clarify the role of p53 in the killing of chronic lymphocytic leukaemia (CLL) cells by purine analogues, we examined the cytotoxic effects of chlorodeoxyadenosine and udarabine on CLL cells that had been characterized according to their p53 functional status.Cases of CLL with p53 dysfunction (n 7) displayed slight, but signi®cant, resistance to nucleoside-induced cell killing when compared with cases with functionally intact p53 (n 12). The small difference between the two groups indicated that p53 plays a minor role in such killing.These ®ndings suggest that the poor therapeutic response to purine analogues observed in patients with p53 defects is likely to be caused by the emergence, on a background of genomic instability, of CLL-cell clones that are resistant to nucleoside-induced killing for reasons unrelated to p53.

No abstract

No abstract