Chronic lymphocytic leukemia and treatment resistance in cancer: the role of the p53 pathway

Abstract

The importance of studying p53 pathway defects in CLL has been fostered by the demonstration of the fundamentally different clinical course of patients with 17p deletion, where the clinical course is, contrary to most patients with CLL, very poor. The demonstration of the resistance to chemotherapy and mutation of the remaining TP53 allele explains the clinical presentation of CLL with 17p deletion. Here we review recent evidence that TP53 mutation in the absence of the deletion of 17p shows a similar clinical and biological course in CLL. In addition, there is growing evidence that alterations of other components of the DNA damage response pathway, such as ATM and miR34a are associated with treatment resistance.