Leukemia Research
Volume 28, Issue 8 , Pages 845-850, August 2004

Treatment of human chronic lymphocytic leukemia cells with the proteasome inhibitor bortezomib promotes apoptosis

  • Todd W Kelley

      Affiliations

    • Department of Clinical Pathology, L11, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA
    • ,
  • Serhan Alkan

      Affiliations

    • Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
    • ,
  • Gordan Srkalovic

      Affiliations

    • Department of Hematology and Medical Oncology and Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA
    • ,
  • Eric D Hsi

      Affiliations

    • Department of Clinical Pathology, L11, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1-216-444-5230; fax: +1-216-444-4414.

Received 12 September 2003; accepted 3 December 2003.

Abstract 

New options are needed for the treatment of B-cell chronic lymphocytic leukemia (CLL). Proteasome inhibitors represent a potential therapeutic strategy. One such agent, bortezomib, was recently approved for the treatment of refractory multiple myeloma. In this study, lymphocytes were isolated from the blood of CLL patients, treated in vitro with bortezomib, and evaluated for apoptosis by flow cytometry. Bortezomib promoted apoptosis in CLL cells in a dose- and time-dependent manner. At 18h incubation time, 10nM bortezomib induced an average 4.27 fold (+/−2.57) increase in the percentage of apoptotic cells versus untreated controls. These data indicate that bortezomib has in vitro activity in CLL and support further investigations of this promising new drug.

Keywords:  Bortezomib, Chronic lymphocytic leukemia, Proteasome inhibitor, NF-kappa B

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PII: S0145-2126(03)00418-1

doi:10.1016/j.leukres.2003.12.010

Leukemia Research
Volume 28, Issue 8 , Pages 845-850, August 2004

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