Bcl-2 antisense therapy in hematologic malignancies

Curr Opin Oncol. 2004 Nov;16(6):581-5. doi: 10.1097/01.cco.0000142074.67968.eb.


Purpose of review: Overexpression of the Bcl-2 oncoprotein is noted in various malignant disorders. In patients with hematologic malignancies, increased production of the Bcl-2 oncoprotein is associated with chemotherapy resistance, aggressive clinical course, and poor survival. Bcl-2 is an important molecular target. Downregulating Bcl-2 can potentially reverse inherent tumor resistance to, and possibly improve response to therapy. This review focuses on the preclinical data, as well as the current clinical information available on oblimersen, a novel antisense approach targeting Bcl-2 in malignant hematologic disorders.

Recent findings: Early clinical trials have shown single-agent activity of oblimersen in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma, and thus, provide proof of principle for antisense therapy. Phase I and phase II studies using oblimersen in combination with conventional chemotherapy have shown encouraging results in patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute myeloid leukemia. Phase III studies in patients with multiple myeloma and chronic lymphocytic leukemia have completed accrual and results are awaited.

Summary: Bcl-2 is a clinically meaningful target in patients with hematologic malignancies. Downregulation of the Bcl-2 oncoprotein can be achieved with oblimersen (antisense molecule specific for Bcl-2). Early clinical results suggest a possible role of this antisense approach in targeting Bcl-2. Ongoing clinical trials will establish the clinical utility of oblimersen in patients with hematologic malignancies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Oligonucleotides, Antisense / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / therapeutic use*


  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2