Targeting cholesterol homeostasis in hematopoietic malignancies

Cholesterol is a vital lipid for cellular functions. It is necessary for membrane biogenesis, cell proliferation, and differentiation. In addition to maintaining cell integrity and permeability, increasing evidence indi-cates a strict link between cholesterol homeostasis, inflammation, and hematological tumors. This makes cholesterol homeostasis an optimal therapeutic target for hematopoietic malignancies. Manipulating cholesterol homeostasis by either interfering with its synthe-sis or activating the reverse cholesterol transport via the engagement of liver X receptors affects the integrity of tumor cells both in vitro and in vivo. Cho-lesterol homeostasis has also been manipulated to restore antitumor immune responses in preclinical models. These observations have prompted clinical tri-als involving acute myeloid leukemia to test the com-bination of chemotherapy with drugs interfering with cholesterol synthesis (ie, statins). We review the role of cholesterol homeostasis in hematopoietic malignan-cies as well as in cells of the tumor microenvironment and discuss the potential use of lipid modulators for therapeutic purposes.