Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia.

@article{Kojima2006Mdm2IN,
  title={Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia.},
  author={Kensuke Kojima and Marina Konopleva and Teresa S. McQueen and Sallyann O'Brien and William Plunkett and Michael Andreeff},
  journal={Blood},
  year={2006},
  volume={108 3},
  pages={
          993-1000
        }
}
Although TP53 mutations are rare in B-cell chronic lymphocytic leukemia (CLL), Mdm2 overexpression has been reported as an alternative cause of p53 dysfunction. We investigated the potential therapeutic use of nongenotoxic p53 activation by a small-molecule antagonist of Mdm2, Nutlin-3a, in CLL. Nutlin-3a induced significant apoptosis in 30 (91%) of 33 samples from previously untreated patients with CLL; all resistant samples had TP53 mutations. Low levels of Atm (ataxia telangiectasia mutated… CONTINUE READING
BETA

Citations

Publications citing this paper.
SHOWING 1-10 OF 79 CITATIONS

FILTER CITATIONS BY YEAR

2006
2018

CITATION STATISTICS

  • 6 Highly Influenced Citations

  • Averaged 5 Citations per year over the last 3 years

Similar Papers

Loading similar papers…