Figure 7. Summary of CXCL12-mediated Signaling in CLL.

Signaling diagram depicting pathways activated downstream of CXLC12. Through direct or indirect mechanisms, arrows indicate factors that are activated, red lines ending with a bar indicate factors that are inhibited by the upstream factor, and lines (no arrowhead) indicate interactions. Proteins in hexagons were identified and validated herein or were previously known targets also detected in the LC-MS/MS. Proteins in rectangles are known key signaling molecules of these pathways that were not detected in this LC-MS/MS data set. Proteins in ovals with dashed lines are likely intermediates/targets of the pathways based on previous studies. Proteins in oval shape were also identified by LC-MS/MS but have yet to be validated. Much of our focus has been on the PI3K/Akt and Raf/MEK/ERK pathways due to known implications in CLL cell survival and resistance to apoptosis. Furthermore, the potential involvement of the p38-MAPK pathway in some CLL patients with activation of HSP27 and LSP1 is outlined.