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International Journal of Hematology

, Volume 92, Issue 3, pp 451–462 | Cite as

Overexpression of PAX5 induces apoptosis in multiple myeloma cells

  • Maryse Proulx
  • Marie-Pierre Cayer
  • Mathieu Drouin
  • André Laroche
  • Daniel JungEmail author
Original Article

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.

Keywords

Multiple myeloma PAX5 Apoptosis Adenovirus Plasma cell leukemia 

Notes

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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Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Maryse Proulx
    • 1
    • 2
  • Marie-Pierre Cayer
    • 1
  • Mathieu Drouin
    • 1
  • André Laroche
    • 1
  • Daniel Jung
    • 1
    • 2
    Email author
  1. 1.Héma-QuébecQuebecCanada
  2. 2.Department of Biochemistry and MicrobiologyLaval UniversityQuebecCanada

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