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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Marom
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A F
authors.initials: AF
authors.lastname: Barak
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: M P
authors.initials: MP
authors.lastname: Kramer
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: H
authors.initials: H
authors.lastname: Lewinsky
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Binsky-Ehrenreich
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Tsitsou-Kampeli
authors.affiliation: Department of Veterinary Resources Weizmann Institute of Science, Rehovot, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Kalchenko
authors.affiliation: Department of Veterinary Resources Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Kuznetsov
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: V
authors.initials: V
authors.lastname: Mirkin
authors.affiliation: Department of Hematology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Dezorella
authors.affiliation: Department of Hematology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shapiro
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MA, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Schwartzberg
authors.affiliation: Department of Hematology, Sanz medical Center, Laniado Medical Center, Netanya, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Shvidel
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Haran
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Becker-Herman
authors.affiliation: Department of Hematology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Herishanu
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Shachar
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000096:biosynthesis*; D059016:Tumor Microenvironment
chemical_list: C498970:CD84 protein, human; C498971:Cd84 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family