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

Cell Cycle. 2008 Dec 15;7(24):3810-4. doi: 10.4161/cc.7.24.7245. Epub 2008 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, Pair 17
  • DNA Damage
  • DNA-Binding Proteins / genetics
  • Drug Resistance, Neoplasm
  • Gene Deletion
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • MicroRNAs / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases