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Lymphoma

Interleukin-21 effectively induces apoptosis in mantle cell lymphoma through a STAT1-dependent mechanism

Leukemia volume 23, pages 1836–1846 (2009)Cite this article

Abstract

Interleukin-21 (IL-21) has been recently shown to modulate the growth of specific types of B-cell neoplasm. Here, we studied the biological effects of IL-21 in mantle cell lymphoma (MCL). All MCL cell lines and tumors examined expressed the IL-21 receptor. Addition of recombinant IL-21 (rIL-21) in vitro effectively induced STAT1 activation and apoptosis in MCL cells. As STAT1 is known to have tumor-suppressor functions, we hypothesized that STAT1 is important in mediating IL-21-induced apoptosis in MCL cells. In support of this hypothesis, inhibition of STAT1 expression using siRNA significantly decreased the apoptotic responses induced by IL-21. To further investigate the mechanism of IL-21-mediated apoptosis, we employed oligonucleotide arrays to evaluate changes in the expression of apoptosis-related genes induced by rIL-21; rIL-21 significantly upregulated three proapoptotic proteins (BIK, NIP3 and HARAKIRI) and downregulated two antiapoptotic proteins (BCL-2 and BCL-XL/S) as well as tumor necrosis factor-α. Using an ELISA-based assay, we demonstrated that rIL-21 significantly decreased the DNA binding of nuclear factor-κB, a transcriptional factor known to be a survival signal for MCL cells. To conclude, IL-21 can effectively induce apoptosis in MCL via a STAT1-dependent pathway. Further understanding of IL-21-mediated apoptosis in MCL may be useful in designing novel therapeutic approaches for this disease.

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Acknowledgements

This study is supported by research grants from the Alberta Cancer Foundation and the Canadian Cancer Society to RL. PG is a recipient of a fellowship award from the Lymphoma Foundation of Canada.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada

    P Gelebart, Z Zak, M Anand, J Dien-Bard & R Lai

  2. Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    H M Amin

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  1. P Gelebart
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Correspondence to R Lai.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Gelebart, P., Zak, Z., Anand, M. et al. Interleukin-21 effectively induces apoptosis in mantle cell lymphoma through a STAT1-dependent mechanism. Leukemia 23, 1836–1846 (2009). https://doi.org/10.1038/leu.2009.100

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