CD84 is a survival receptor for CLL cells

Abstract

Chronic lymphocytic leukemia (CLL) is a malignancy of mature lymphocytes that is manifest by the progressive accumulation of transformed cells, mostly due to their decreased apoptosis. CD84 belongs to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors and has an as yet unknown function in normal B cells and CLL lymphocytes. We show that CD84 is over-expressed in CLL cells. Activation of cell surface CD84 initiates a signaling cascade, which enhances cell survival. Both immunoneutralization or blockade of CD84 induce cell death in vitro and in vivo. Thus, overexpression of CD84 from an early stage may be critical for the survival of CLL. These findings suggest novel therapeutic strategies based on the blockade of a CD84 dependent survival pathway.

CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia

“…It is a cell-surface protein that forms homophilic dimers by selfassociation (7)(8)(9). Our studies have previously characterized a survival pathway in CLL regulated by CD84 (10). In addition, we recently showed that CD84 serves as an important bridge mediating the interaction between CLL cells and the various cells in their microenvironment in vitro and in vivo (11).…”

T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell–Cell Contact Mediated through SLAMF6 and SAP

“…Additional SLAM family members have been implicated in survival of specific B cell populations; SLAMF5 (CD84) induces survival of CLL cells, which upregulate its expression in a CD74/MIF dependent manner (12, 33). SLAMF1 (CD150) regulates apoptosis, proliferation and differentiation and IgG synthesis of B cells (44, 45).…”

“…Purified T cells and B cells (5×10 6 ) were subjected to electroporation as previously described (12). The cells were treated with the following siRNAs: SAP, NTB- A, CD74 (ON-TARGET plus SMART pool) and negative control siRNA (ON-TARGET plus non-targeting pool) (Dharmacon).…”

“…Immunoprecipitation of endogenously expressed proteins and their detection were performed on fresh mouse lymphocytes as previously described (12). For IP and Blotting of EAT2, anti-EAT-2 Ab (N-14; Santa cruz) was used.…”

“…To define the molecules whose expression is modulated by CD74 to regulate CLL cell survival, we previously screened for CD74 target genes. One molecule, whose expression was strongly upregulated by CD74 activation, is SLAMF5 (CD84), a member of the Signaling lymphocytic activation molecule (SLAM) immunoglobulin superfamily (12). …”