BCL2 and neoplasm: Extrinsic mechanisms are mainly mediated by interactions with the bone marrow (BM) microenvironment (7, 19), cell adhesion to the extracellular matrix (ECM), and other elements of the tumor microenvironment (20), which may induce the production in MM cells of cell cycle inhibitors, anti-apoptotic members of the Bcl-2 family, and ABC drug transporters (21) (18, 22) as well as the release of soluble factors, such as interleukin (IL)-6 and insulin-like growth factor (IGF)-1, by bone marrow stromal cells (BMSCs) that activate the signal transduction pathways leading to drug resistance (23).