NF-kappaB as a therapeutic target in chronic lymphocytic leukemia

Expert Opin Ther Targets. 2010 Mar;14(3):275-88. doi: 10.1517/14728221003598930.


Importance of the field: NF-kappaB includes a family of transcription factors that play a critical role in the biology of normal lymphocytes and it is aberrantly activated in chronic lymphocytic leukemia (CLL) cells. Here, we review the role of constitutive NF-kappaB activation in CLL pathogenesis and its potential as a therapeutic target for CLL treatment.

Areas covered in this review: This review highlights the different strategies reported to inhibit NF-kappaB signaling in CLL cells. They include both IkappaB kinase inhibitors and several natural compounds that act at different steps of the pathway.

What the reader will gain: Targeting NF-kappaB leads to apoptosis of CLL cells, corroborating the role of NF-kappaB in the survival and clonal expansion of these tumoral cells. Moreover, several studies confirmed a synergistic effect between NF-kappaB inhibitors and other antitumoral agents and that inhibition of NF-kappaB could overcome the microenvironmental protection of CLL cells.

Take home message: NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival pathway, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Drug Delivery Systems*
  • Drug Synergism
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / physiopathology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects


  • Antineoplastic Agents
  • NF-kappa B
  • I-kappa B Kinase