Role of BM blood vessels in myeloid malignancies. Angiogenesis increases during progression of myeloid malignancies and is particularly associated with fibrotic stages of the disease. Leukemic cells produce angiogenic factors such as VEGF and inflammatory cytokines (blue arrows) to stimulate proliferation of ECs, expression of adhesion molecules, and secretion of angiocrine factors. EC-derived angiocrine factors (red arrows) stimulate leukemic cell proliferation and survival, triggering a vicious cycle to remodel the BM into a self-reinforcing niche. OB, osteoblast.