Schematic representation of leukemic cell−BM-MSC cross-talk. Interactions of leukemic cells with BM-MSCs promote transcriptional changes in the BM stroma that ultimately impact leukemic cells proliferation and survival. Activation of NF-κB and transcription of NF-κB downstream target genes (IL-8, IL-6, CCL2, and VCAM-1, etc.) are triggered in BM-MSCs by these interactions. Communication between these 2 cell types can be achieved by integrins and their receptors (ie, VCAM-1/VLA-4) or by soluble factors that are directly secreted to the extracellular milieu (such as IL-1). VCAM-1/VLA-4 interaction between leukemia cells and BM-MSC may provide a possible mechanism for the activation of NF-κB in both BM-MSCs and leukemia cells.