PIM inhibitor not only directly targets CLL cells, but also abrogates the cross‐talk between leukaemic cells and their microenvironment by impairing CXCR4‐CXCL12 interaction and mTOR activity, leading to detachment of CLL cell from the niche and facilitating apoptosis. Here, CXCR4 is linked to B-cell chronic lymphocytic leukemia.