Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world; characterized by the progressive accumulation of small, mature CD5+ B lymphocytes in the peripheral blood, lymphoid organs and bone marrow (BM). Unlike other leukemias, the main feature of the disease is decreased apoptosis, resulting in the pathologic accumulation of these malignant cells.
Our lab characterized CD74 as a survival receptor expressed on these leukemic cells. In our search for genes whose expression is modulated by CD74, we identified the cell surface molecule CD84.
CD84 is expressed on all hematopoietic cells as well as on CLL cells, where its expression is elevated from the early stages of the disease. We showed that activation of CD84 leads to survival of CLL cells in vitro and in vivo. Blocking CD84 using anti-CD84 blocking antibodies, which was generated in our lab, induced CLL cell death.
Our lab is currently studying the role of CD84 in mediating interaction of CLL cells with their survival supporting microenvironment.
The interplay between chronic lymphoid leukemia (CLL) and the microenvironment via CD84
CD84 regulates the interaction of CLL cells with their microenvironment and the ECM
Exploring the role of Slam family members in survival of multiple myeloma
X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by infection with Epstein-Barr virus. XLP is clinically characterized by three major phenotypes: fulminant infectious mononucleosis (FIM) (50%), B cell lymphomas (20%), or dys-gammaglobulinemia (30%). Most patients with XLP die by the age of 40 and more than 70% of patients die before the age of ten. Mutations in the SAP, a signaling adaptor molecule, underlie in most cases of familial XLP.
Our study aims to determine the mechanism that governs the B cell repertoire and function in XLP patients. In these experiments, we analyze B cells derived from peripheral blood (PB) of XLP patients and healthy human control subjects. In parallel, to address the question of whether SAP plays a role in B-cell function we are also examining B cells derived from SAP deficient mice.
Overall, our findings illuminate several interesting aspects of signaling and function into the pathology of the XLP disease. Moreover, it raises the possibility that in the future manipulation of SAP-mediated signaling pathways may have therapeutic benefits.
B cell-T cell signaling through SAP is essential for the maintenance of peripheral B cell populations