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Overexpression of PAX5 induces apoptosis in multiple myeloma cells

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Abstract

PAX5 is an essential transcription factor for the commitment of lymphoid progenitors to the B-lymphocyte lineage. PAX5 suppression results in retrodifferentiation of B lymphocytes to an uncommitted progenitor cell stage, whereas PAX5 suppression in mature B lymphocytes leads to further development into plasma cells. Here, we have analyzed the fate of plasma cell lines following PAX5 reexpression. Human B cell lines were infected with Ad5/F35 adenoviruses encoding either EYFP or PAX5. Expression analysis of specific plasma cell transcription factors (IRF4, Blimp-1 and XBP-1) suggests that PAX5 reexpression does not induce retrodifferentiation of plasma cells into B lymphocytes. Interestingly, the viability of RPMI-8226 and U266 multiple myeloma cell lines markedly declined at 4–7 days post-transduction, whereas other plasma cell lines maintained their viability. Apoptosis analysis through Annexin V measurement also revealed a higher level of apoptosis in PAX5-expressing myeloma cell lines. Finally, Western blot analysis of pro- and anti-apoptotic proteins revealed that the anti-apoptotic protein MCL-1 was down-modulated in PAX5-transduced multiple myeloma cell lines. In conclusion, our results show that the expression of PAX5 in plasma cell lines induces apoptosis exclusively in multiple myelomas. This might represent a potential therapeutic avenue in the treatment of multiple myeloma.

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Acknowledgments

Maryse Proulx is supported by a scholar grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). We are grateful to Jean-François Leblanc for its comments on the manuscript.

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Authors and Affiliations

  1. Héma-Québec, 1070 av. des Sciences-de-la-Vie, Quebec, G1V 5C3, QC, Canada

    Maryse Proulx, Marie-Pierre Cayer, Mathieu Drouin, André Laroche & Daniel Jung

  2. Department of Biochemistry and Microbiology, Laval University, Quebec, QC, Canada

    Maryse Proulx & Daniel Jung

Authors
  1. Maryse Proulx
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  2. Marie-Pierre Cayer
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  3. Mathieu Drouin
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  4. André Laroche
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  5. Daniel Jung
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Correspondence to Daniel Jung.

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Proulx, M., Cayer, MP., Drouin, M. et al. Overexpression of PAX5 induces apoptosis in multiple myeloma cells. Int J Hematol 92, 451–462 (2010). https://doi.org/10.1007/s12185-010-0691-9

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  • DOI: https://doi.org/10.1007/s12185-010-0691-9

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