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  • Original Article
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Myeloma

The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells

Leukemia volume 25, pages 1182–1188 (2011)Cite this article

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Abstract

Bone marrow stromal cells (BMSCs) and osteoclasts (OCs) confer multiple myeloma (MM) cell survival through elaborating factors. We demonstrate herein that IL-6 and TNF family cytokines, TNFα, BAFF and APRIL, but not IGF-1 cooperatively enhance the expression of the serine/threonine kinase Pim-2 in MM cells. BMSCs and OCs upregulate Pim-2 expression in MM cells largely via the IL-6/STAT3 and NF-κB pathway, respectively. Pim-2 short interfering RNA reduces MM cell viability in cocultures with BMSCs or OCs. Thus, upregulation of Pim-2 appears to be a novel anti-apoptotic mechanism for MM cell survival. Interestingly, the mammalian target of rapamycin inhibitor rapamycin further suppresses the MM cell viability in combination with the Pim-2 silencing. The Pim inhibitor (Z)-5-(4-propoxybenzylidene) thiazolidine-2, 4-dione and the PI3K inhibitor LY294002 cooperatively enhance MM cell death. The Pim inhibitor suppresses 4E-BP1 phosphorylation along with the reduction of Mcl-1 and c-Myc. Pim-2 may therefore become a new target for MM treatment.

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Acknowledgements

This work was supported in part by Grants-in-aid for Scientific Research (A) to TM and (C) to MA, and for the 21st Century Center of Excellence Program from the Ministry of Education, Culture, Science and Sports of Japan, and a Grant-in-aid for Cancer Research (17–16) to MA from the Ministry of Health, Labor and Welfare of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. J Asano and A Nakano: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan

    J Asano, A Nakano, A Oda, H Amou, K Takeuchi, H Miki, S Nakamura, T Harada, S Fujii, K Kagawa, I Endo, K Yata, T Matsumoto & M Abe

  2. Department of Biomaterials and Bioengineering, University of Tokushima Graduate School of Oral Sciences, Tokushima, Japan

    M Hiasa

  3. Department of Hematology and Oncology, RIRBM, Hiroshima University, Hiroshima, Japan

    A Sakai

  4. Division of Transfusion Medicine, Tokushima University Hospital, Tokushima, Japan

    S Ozaki

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  1. J Asano
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Correspondence to M Abe.

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Supplementary Information accompanies the paper on the Leukemia website

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Asano, J., Nakano, A., Oda, A. et al. The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells. Leukemia 25, 1182–1188 (2011). https://doi.org/10.1038/leu.2011.60

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