Antisense-mediated suppression of Bcl-2 highlights its pivotal role in failed apoptosis in B-cell chronic lymphocytic leukaemia

Br J Haematol. 1999 Dec;107(3):611-5. doi: 10.1046/j.1365-2141.1999.01726.x.


Although advances have been made in the development of more effective treatment modalities, B-cell chronic lymphocytic leukaemia (B-CLL) remains incurable due to the development of drug resistance. Defective programmed cell death mechanisms rather than dysregulation of cell cycle appears to predominate in B-CLL and it is likely that a failure to initiate apoptosis contributes to chemoresistance. Most B-CLL cells contain high levels of the anti-apoptotic protein Bcl-2 and high Bcl-2/Bax ratios have been associated with in vitro resistance to cytotoxic agents. In this study we evaluated the cellular responses to a Bcl-2 antisense oligonucleotide in terms of Bcl-2 mRNA and protein expression and the induction of apoptosis. The antisense molecule induced a specific reduction in Bcl-2 mRNA and protein expression over the 48 h culture period and was associated with increased apoptosis. The study indicates that Bcl-2 protein is central to the mediation of resistance to apoptosis in B-CLL. Therefore Bcl-2 antisense oligonucleotides might be useful in the treatment of B-CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Genes, bcl-2 / genetics*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Oligonucleotides, Antisense / genetics*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • bcl-2-Associated X Protein


  • BAX protein, human
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein