The Role of Chemokines and Receptors in Chronic Lymphocytic Leukemia

HANDEL LAB, UCSD, SKAGGS SCHOOL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Chronic Lymphocytic Leukemia 

Chronic Lymphocytic Leukemia (CLL) is considered a disease originating primarily from immature B-cells that are thought to have an apoptotic defect in vivo, but die rapidly in vitro. The clinical course of CLL is quite variable, and the disease can be characterized as either aggressive which correlates with high ZAP-70 expression (ZAP-70+) on the CLLs or indolent with low/no ZAP-70 (ZAP-70-) expression. CXCL12 has been shown to promote the survival of CLL cells in vitro and possibly in vivo.  Based on preliminary data, part of the mechanism appears to involve activation of pathways implicated in survival including Akt and ERK1/2. However, differences in CXCL12-mediated CLL survival between the two ZAP-70 subgroups have not been characterized, nor have the upstream modulators and downstream molecular targets of Akt and ERK1/2 that may mediate survival effects in these cells. By using a combination of directed immunoblot and global proteomic profiling approaches, the goal of this project is to decipher the molecular mechanisms underlying CXCL12-induced survival signaling and potential differences in signaling between the two subgroups of CLL patients.  

 

Techniques: Proteomics, Tissue Culture, Cell Based Assays