Best Practice & Research Clinical Haematology
Volume 23, Issue 1 , Pages 121-131, March 2010

Signalling to drug resistance in CLL

  • Erin Hertlein, PhD

      Affiliations

    • Division of Hematology-Oncology, College of Medicine, Columbus, OH, USA
  • ,
  • John C. Byrd, MD

      Affiliations

    • Division of Hematology-Oncology, College of Medicine, Columbus, OH, USA
    • Division of Medicinal Chemistry, College of Pharmacy, Columbus, OH, USA
    • The Ohio State Comprehensive Cancer Center, Columbus, OH, USA
    • Corresponding Author InformationCorresponding author. B302 Starling-Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 293-9869; Fax: +1 614 292-3312.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling pathway is constitutively active in a variety of cancers, including chronic lymphocytic leukaemia (CLL). The importance of this signalling pathway identifies it as a prime therapeutic target; however, the complexity and potential side effects of inhibiting NF-κB have thus far made the clinical use of NF-κB inhibitors a relatively unexplored resource in this disease. This article discusses the role of NF-κB in CLL as a common crossroad for pathways promoting drug resistance in CLL. We provide the background on how this pathway contributes to both spontaneous and drug-induced apoptosis. Potential new avenues to regulate this pathway in CLL are also discussed.

Keywords: chronic lymphocytic leukaemia, NF-κB, drug resistance

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 This work was supported by the CALGB Foundation, D. Warren Brown Foundation, Specialized Center of Research from the Leukemia and Lymphoma Society, P01 CA95426, T325CA009338, T32 CA106196 and P01 CA101956 from National Cancer Institute.

PII: S1521-6926(10)00008-3

doi:10.1016/j.beha.2010.01.007

Best Practice & Research Clinical Haematology
Volume 23, Issue 1 , Pages 121-131, March 2010