BCL2 and neoplasm: Indeed, intrinsic defects in the apoptotic machinery such as overexpression of BCL-2 and myeloid-cell leukemia 1 (MCL-1) anti-apoptotic members, or impaired expression of pro-apoptotic members (Bax and Bak), and extrinsic factors consisting mainly of stromal cell–derived cytokines and chemokines (e.g. CXCL12), provide survival cues during which tumor cells transit through lymphoid tissues and tilt the balance toward prolonged lifespan of CLL B cells (6, 26).