miR-21 targets SPRY2 in human CLL cells to activate BCR-mediated MAPK-Erk signaling. (A) Scanned western blot showing SPRY2 protein levels in miR-21–overexpressing CLL cells; β-actin was used as loading control. (B) Protein levels of p-Erk and Erk in miR-21–overexpressing cells, and densitometric measurements showing elevated levels of p-Erk in miR-21–overexpressing CLL cells. (C) Scanned western blot showing the protein levels of p-Syk, Syk, and SPRY2 in miR-21–overexpressing Mec-1 CLL cells. (D) In the case of nB cells (left), BCR stimulation leads to activation of MAPK-Erk signaling, which results in their proliferation and survival. As a homeostasis response, SPRY2 gets induced to regulate signaling in activated B cells. Whereas in the case of CLL cells (right), elevated levels of miR-21 leads to decreased SPRY2, which results in constitutive activation of BCR and MAPK-Erk signaling. This in turn increases the proliferation and survival of CLL cells.