Targeting cholesterol homeostasis in hematopoietic malignancies

被引：22

作者：

Brendolan, Andrea ^{[1
]}

Russo, Vincenzo ^{[2
]}

机构：

[1] IRCCS Sci Inst San Raffaele, Lymphoid Organ Dev Unit, Milan, Italy

[2] IRCCS Sci Inst San Raffaele, Div Expt Oncol, Immunobiotherapy Melanoma & Solid Tumors Unit, Milan, Italy

来源：

BLOOD | 2022年 / 139卷 / 02期

关键词：

LIVER-X RECEPTORS; LOVASTATIN-INDUCED APOPTOSIS; MYELOID-LEUKEMIA CELLS; MEVALONATE PATHWAY; NUCLEAR RECEPTORS; LIPID-METABOLISM; GENE-EXPRESSION; DENDRITIC CELLS; SMALL-MOLECULE; LXR;

D O I：

10.1182/blood.2021012788

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：165 / 176

页数：12

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