Figure 6.

Schematic illustration of IL‐6‐mediated activation of STAT3 and NF‐κB. After engagement with receptor CD126, IL‐6 activates JAK2, which induces diverse signaling pathways: (1) activates STAT3 by inducing STAT3 phosphorylation, mitochondrial and nuclear translocation; (2) activates PI3K/AKT axis, which induces NF‐κB activation. Both activated STAT3 and NF‐κB induce expression of Bcl‐xL and Mcl‐1. Increased expression and Bcl‐xL and Mcl‐1 in the mitochondria, together with mitochondrial STAT3, prevent mitochondria‐dependent apoptosis and promote CLL cell survival. CLL: chronic lymphocytic leukemia [Color figure can be viewed at wileyonlinelibrary.com]