Figure 1.

The CLL microenvironmental signalosome: the convergence of microenvironmental-induced signaling responses into biochemical pathways within CLL cells. Microenvironmental elements ( ) including cells (e.g. T-cells, nurse-like cells), the extracellular matrix (ECM) and enzymes (e.g. MMP9) stimulate CLL cells either directly (arrows) or via mediators such as cytokines and chemokines (dashed arrows). These extracellular triggers converge into an array of intracellular biochemical responses ( ), resulting in the up-regulation of MYC and anti-apoptotic proteins ( ), as well as additional cellular responses.