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Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner

Oncogene volume 39, pages 1997–2008 (2020)Cite this article

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Abstract

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B lymphocytes. The microenvironment of the CLL cells is a vital element in the regulation of the survival of these malignant cells. CLL cell longevity is dependent on external signals, originating from cells in their microenvironment including secreted and surface-bound factors. Dendritic cells (DCs) play an important part in tumor microenvironment, but their role in the CLL bone marrow (BM) niche has not been studied. We show here that CLL cells induce accumulation of bone marrow dendritic cells (BMDCs). Depletion of this population attenuates disease expansion. Our results show that the support of the microenvironment is partly dependent on CD84, a cell surface molecule belonging to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors. Our results suggest a novel therapeutic strategy whereby eliminating BMDCs or blocking the CD84 expressed on these cells may reduce the tumor load.

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Data availability

The RNAseq results were submitted to GEO (GSE119115).

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Acknowledgements

The authors wish to thank members of the Shachar lab for fruitful discussion and support. IS is the incumbent of the Dr Morton and Ann Kleiman Professorial Chair. This research was supported by the DKFZ-MOST cooperation in cancer research, ERA-NET TRANSCAN-2 program JTC 2014–project FIRE-CLL and the Binational Science Foundation (BSF) grant no 711979. This research was performed without the support of the Israel Science Foundation.

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Authors and Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel

    Avital F. Barak, Hadas Lewinsky, Michal Perpinial, Victoria Huber, Lihi Radomir, Mattias P. Kramer, Lital Sever, Yochai Wolf, Steffen Jung, Shirly Becker-Herman & Idit Shachar

  2. Department of Hematology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Mika Shapiro & Yair Herishanu

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  1. Avital F. Barak
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Author contributions

AFB—designed research, performed research, analyzed data and wrote the paper. HL—designed research, performed research and analyzed data. MP—designed research, performed research and analyzed data. VH—designed research, performed research and analyzed data. LR—designed research, performed research and analyzed data. MPK—designed research, performed research and analyzed data. LS—performed research, analyzed data. YW—designed research and contributed vital reagent. MS—designed research and contributed vital reagent. YH—designed research and contributed vital reagent. SJ—designed research, contributed vital reagent and wrote the paper. SB-H—designed research, performed research, analyzed data. IS—designed research, analyzed data, and wrote the paper.

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Correspondence to Idit Shachar.

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Barak, A.F., Lewinsky, H., Perpinial, M. et al. Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner. Oncogene 39, 1997–2008 (2020). https://doi.org/10.1038/s41388-019-1121-y

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