CLL cells constitutively express functional CXCR4 [11] which, upon the binding with CXCL12 (also known as stromal cell–derived factor-1, SDF-1), activates a multitude of intracellular pathways, including ERK1-2 and PI3K/AKT, whose inhibition overcomes SC-mediated drug resistance [12,13]. The gene discussed is CXCL12; the disease is B-cell chronic lymphocytic leukemia.