CD84 mediates CLL-microenvironment interactions

A. Marom; A. F. Barak; M. P. Kramer; H. Lewinsky; I. Binsky-Ehrenreich; S. Cohen; A. Tsitsou-Kampeli; V. Kalchenko; Y. Kuznetsov; V. Mirkin; N. Dezorella; M. Shapiro; P. L. Schwartzberg; Y. Cohen; L. Shvidel; M. Haran; S. Becker-Herman; Y. Herishanu; I. Shachar

doi:10.1038/onc.2016.238

CD84 mediates CLL-microenvironment interactions

A. Marom, A. F. Barak, M. P. Kramer, H. Lewinsky, I. Binsky-Ehrenreich, S. Cohen, A. Tsitsou-Kampeli, V. Kalchenko, Y. Kuznetsov, V. Mirkin, N. Dezorella, M. Shapiro, P. L. Schwartzberg, Y. Cohen, L. Shvidel, M. Haran, S. Becker-Herman, Y. Herishanu, I. Shachar^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English
Pages (from-to)	628-638
Number of pages	11
Journal	Oncogene
Volume	36
Issue number	5
DOIs	https://doi.org/10.1038/onc.2016.238
State	Published - 2 Feb 2017
Externally published	Yes

Funding

Funders	Funder number
National Human Genome Research Institute	ZIAHG000123

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2016.238

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Marom, A., Barak, A. F., Kramer, M. P., Lewinsky, H., Binsky-Ehrenreich, I., Cohen, S., Tsitsou-Kampeli, A., Kalchenko, V., Kuznetsov, Y., Mirkin, V., Dezorella, N., Shapiro, M., Schwartzberg, P. L., Cohen, Y., Shvidel, L., Haran, M., Becker-Herman, S., Herishanu, Y., & Shachar, I. (2017). CD84 mediates CLL-microenvironment interactions. Oncogene, 36(5), 628-638. https://doi.org/10.1038/onc.2016.238

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title = "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.",

author = "A. Marom and Barak, {A. F.} and Kramer, {M. P.} and H. Lewinsky and I. Binsky-Ehrenreich and S. Cohen and A. Tsitsou-Kampeli and V. Kalchenko and Y. Kuznetsov and V. Mirkin and N. Dezorella and M. Shapiro and Schwartzberg, {P. L.} and Y. Cohen and L. Shvidel and M. Haran and S. Becker-Herman and Y. Herishanu and I. Shachar",

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Marom, A, Barak, AF, Kramer, MP, Lewinsky, H, Binsky-Ehrenreich, I, Cohen, S, Tsitsou-Kampeli, A, Kalchenko, V, Kuznetsov, Y, Mirkin, V, Dezorella, N, Shapiro, M, Schwartzberg, PL, Cohen, Y, Shvidel, L, Haran, M, Becker-Herman, S, Herishanu, Y & Shachar, I 2017, 'CD84 mediates CLL-microenvironment interactions', Oncogene, vol. 36, no. 5, pp. 628-638. https://doi.org/10.1038/onc.2016.238

TY - JOUR

T1 - CD84 mediates CLL-microenvironment interactions

AU - Marom, A.

AU - Barak, A. F.

AU - Kramer, M. P.

AU - Lewinsky, H.

AU - Binsky-Ehrenreich, I.

AU - Cohen, S.

AU - Tsitsou-Kampeli, A.

AU - Kalchenko, V.

AU - Kuznetsov, Y.

AU - Mirkin, V.

AU - Dezorella, N.

AU - Shapiro, M.

AU - Schwartzberg, P. L.

AU - Cohen, Y.

AU - Shvidel, L.

AU - Haran, M.

AU - Becker-Herman, S.

AU - Herishanu, Y.

AU - Shachar, I.

PY - 2017/2/2

Y1 - 2017/2/2

N2 - 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.

AB - 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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JO - Oncogene

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IS - 5

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CD84 mediates CLL-microenvironment interactions

Abstract

Funding

UN SDGs

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