Journal of Molecular Medicine

, Volume 86, Issue 5, pp 541–552

Arsenic trioxide induces apoptosis preferentially in B-CLL cells of patients with unfavourable prognostic factors including del17p13

  • Olaf Merkel
  • Christoph Heyder
  • Daniela Asslaber
  • Frank Hamacher
  • Inge Tinhofer
  • Claudia Holler
  • Markus Stöcher
  • Andreas Prokesch
  • Christine Papak
  • Marcel Scheideler
  • Zlatko Trajanoski
  • Richard Greil
Original Article

Abstract

In the last decade, arsenic trioxide (As2O3) has been used very successfully to treat acute promyelocytic leukaemia (APL). Much less is known about the effectiveness of As2O3 in other neoplastic disorders. In this paper, we report that after 18 h in vitro treatment with 4 μM As2O3, 75 ± 18% of B cell chronic lymphocytic leukaemia (B-CLL) cells (n = 52) underwent apoptosis. It is important to note that B-CLL cells harboring a deletion of chromosome 17p13, which predisposes to fludarabine resistance and has been identified as an important negative predictor of clinical outcome, were more susceptible to As2O3 toxicity than cells lacking this aberration. Furthermore, unfavourable risk profiles such as unmutated IgVH status, high CD38 expression and prior treatment were associated with significantly higher sensitivity of B-CLL cells to As2O3. As2O3 also preferentially killed B-CLL cells compared to B cells from healthy age-matched controls. Molecular analysis revealed that basal superoxide dismutase activity was positively correlated with the pro-apoptotic activity of As2O3 pointing to a role of reactive oxygen species in cell death induction. The high activity of As2O3 in B-CLL cells from high-risk patients makes it a promising drug for high-risk and/or fludarabine-refractory B-CLL patients.

Keywords

Arsenic Reactive oxidants Leukaemia Lymphocyte 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Olaf Merkel
    • 1
    • 3
  • Christoph Heyder
    • 1
  • Daniela Asslaber
    • 1
  • Frank Hamacher
    • 1
  • Inge Tinhofer
    • 1
  • Claudia Holler
    • 1
  • Markus Stöcher
    • 1
  • Andreas Prokesch
    • 2
  • Christine Papak
    • 2
  • Marcel Scheideler
    • 2
  • Zlatko Trajanoski
    • 2
  • Richard Greil
    • 1
  1. 1.Laboratory for Immunological and Molecular Cancer Research, IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and InfectiologyParacelsus Medical University SalzburgSalzburgAustria
  2. 2.Institute for Genomics and BioinformaticsGraz University of TechnologyGrazAustria
  3. 3.LIMCRParacelsus Medical UniversitySalzburgAustria

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