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Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations

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Abstract

Background

B-cell chronic lymphocytic leukemia (B-CLL) is a remarkably heterogeneous disorder. Some patients have an indolent disease whereas others undergo a more agressive presentation needing treatment. New therapeutics approaches are necessary for the treatment of B-CLL. Bortezomib (Btz), is a proteasome inhibitor, currently undergoing clinical trials whose function, at least in part, by stabilizing the I⦊Bα protein and inhibiting NF⦊B activation.

Objective

The objective of this work was to study the effects of Btz on isolated human B-CLL cells,in vitro, and to correlate the differential rates of apoptosis induction with biological variables.

Material and methods

31 B-CLL samples, from patients in stage A of Binet were used for this study, and the apoptotic effect of Btz on these cells was measured.

Results

Our data show that Btz treatment of B-CLL cells induces apoptosis in a time and dose-dependent manner: The apoptosis induction is mediated in part by inhibition of NF⦊B and is dependent on caspases activation. Interesting, in IgVH mutated cells, Btz have statistically significant differences in theirin vitro activity on B-CLL cells according to their BCL-6 mutational status.

Conclusions

Btz is a promising pharmacologic agent for the treatment of B-CLL, but its efficacy seems to be related to IgVH and BCL-6 mutational status, therefore, it could be interesting to further investigate the mechanisms involved in the different behavior of the cells in response to apoptosis induction by this drug.

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Authors and Affiliations

  1. Hospital Clínico Universitario de Valencia, Valencia, Spain

    Eloisa Jantus-Lewintre, Elena Sarsotti, María José Terol & Isabel Benet

  2. Universidad de Valencia, Valencia, Spain

    Javier García-Conde

  3. Laboratorio de Hematología Molecular, Centro de Investigación Príncipe Felipe, Avda. Autopista El Saler, 16-3, 46013, Valencia, Spain

    Eloisa Jantus-Lewintre & Javier García-Conde

Authors
  1. Eloisa Jantus-Lewintre
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  2. Elena Sarsotti
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  3. María José Terol
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  4. Isabel Benet
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  5. Javier García-Conde
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Correspondence to Eloisa Jantus-Lewintre.

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Jantus-Lewintre, E., Sarsotti, E., Terol, M.J. et al. Bortezomib induces different apoptotic rates in B-CLL cells according to IgVH and BCL-6 mutations. Clin Transl Oncol 8, 805–811 (2006). https://doi.org/10.1007/s12094-006-0136-3

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  • DOI: https://doi.org/10.1007/s12094-006-0136-3

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