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  • Original Article
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CD84 mediates CLL-microenvironment interactions

Abstract

Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes. Signals from the CLL microenvironment promote progression of the disease and induce drug resistance. This phenomenon is largely dependent on direct contact between the malignant B cells and stromal cells. CD84 belongs to the signaling lymphocyte activation molecule family of immunoreceptors, which self-associates, forming an orthogonal homophilic dimer. We therefore hypothesized that CD84 may bridge between CLL cells and their microenvironment, promoting cell survival. Our in vitro results show that CD84 expressed on CLL cells interact with CD84 expressed on cells in their microenvironment, inducing cell survival in both sides. Blocking CD84 in vitro and in vivo disrupt the interaction of CLL cells with their microenvironment, resulting in induced cell death. Thus, our findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.

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Acknowledgements

We thank members of the Shachar laboratory for fruitful discussion and support. IS is the incumbent of the Dr Morton and Ann Kleiman Professorial Chair. This research was supported by the Israel Science Foundation, Israel Cancer association, Israel Cancer Research Fund (ICRF), DKFZ-MOST cooperation in cancer research, Quinquin foundation and Rubenstein charitable foundation.

Author contributions

AM, AFB, MPK, HL, IB-E ans SC- designed the research, performed the reserach and analyzed the data and wrote the paper. AT-K, VK, YK performed the research and analyzed the data. VM, ND, MS, PLS and LS contributed the vital reagent. YC performed the research, contributed the vital reagent. MH and YH contributed the vital reagent and designed the research. IS designed the research, analyzed the data and wrote the paper.

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Correspondence to I Shachar.

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Marom, A., Barak, A., Kramer, M. et al. CD84 mediates CLL-microenvironment interactions. Oncogene 36, 628–638 (2017). https://doi.org/10.1038/onc.2016.238

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