Within the TME, CLL cells secrete cytokines and chemokines which sustain and fuel pro-tumorigenic loops [13–15], as exemplified by Interleukin (IL)-10, that suppresses the ability of monocytes/macrophages to produce TNF-α [16], and IL-9, released by CLL cells from patients with aggressive disease, that stimulates stromal cells to secrete homing chemokines, which in turn contribute to attract CLL cells to the pro-survival lymphoid niche [15, 17]. The gene discussed is TNF; the disease is B-cell chronic lymphocytic leukemia.