Figure 1: Bone marrow milieu is abundant with CXCL12 (SDF1) secreted by local stromal cells. CXCL12 is a ligand for CXCR4 receptors. Abundant CXCL12 primes circulating plasma cells for homing by upregulating transcription of CXCR4 and integrins. These primed plasma cells are attracted towards CXCL12-rich bone marrow stroma. Increased expression of integrins on plasma cells facilitates their extravasation in the bone marrow. In the bone marrow, CXCL12-CXCR4 axis promotes survival of malignant plasma cells through regulation of several survival signaling cascades such as PI3κ, NFκB and MAPκ. Targeting CXCR4 by specific blocκers will inhibit homing of malignant plasma cells and their survival in the bone marrow.