Malignant cells alter the HSC niche. Malignant (Malig) cells secrete factors including CCL3 and IL1β that, directly or through monocytic cells (here shown as macrophages) or sympathetic nerves, respectively, target multiple stromal cell populations implicated in the HSC niche, including CAR cells and osteoblasts (Ob). This results in decreased stromal cell CXCL12 expression and potentially other changes, which in turn, increase niche support of malignant cells over normal HSCs.