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The effect of p53 dysfunction on purine analogue cytotoxicity in chronic lymphocytic leukaemia
Author(s) -
Pettitt,
Sherrington,
Cawley
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01649.x
Subject(s) - fludarabine , purine analogue , chronic lymphocytic leukemia , cladribine , cytotoxicity , purine , nucleoside , cancer research , nucleoside analogue , immunology , dna damage , cytotoxic t cell , biology , medicine , leukemia , dna , chemotherapy , genetics , biochemistry , in vitro , enzyme , cyclophosphamide
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 fludarabine on CLL cells that had been characterized according to their p53 functional status. Cases of CLL with p53 dysfunction ( n = 7) displayed slight, but significant, 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 findings 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.