BM alterations and emerging niche-targeted therapeutic strategies in myeloid malignancies. This schema summarizes the most recurrent niche changes observed in human myeloid malignancies and the pharmacological approaches being explored to target niche-leukemia interdependencies. Depicted niche changes reflect mesenchymal, neurological, and endothelial niche remodeling. Pharmacological approaches include strategies to revert vascular leakiness (eg, NO synthase inhibitors)¹¹³  and prevent nerve damage (eg, IL-1 antagonists, and neuroprotective agents such as 4-methylcatechol [4-MC]) or its impact on MSCs (β3-AR agonists, such as mirabegron in phase II clinical trial in MPN [identifier NCT02311569]).^84,96  Approaches to prevent or overcome therapeutic resistance include the inhibition of the FAO by blocking the function of the rate-limiting enzyme CPT-1 (eg, etomoxir, ranolazine),¹¹⁵  or interfering with mitochondrial function using tigecycline.