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. 2023 May;102(5):1073-1086.
doi: 10.1007/s00277-023-05169-7. Epub 2023 Mar 21.

Lycorine induces apoptosis of acute myeloid leukemia cells and inhibits triglyceride production via binding and targeting FABP5

Xinming Liang #  1 , Wenli Fu #  1 , YuHui Peng  1 , Juanjuan Duan  1 , Ting Zhang  1 , Daogui Fan  1 , Wei Hong  1 , Xiaolan Qi  1 , ChangXue Wu  1 , Yan He  1 , Wenfeng Yu  1 , Jing Zhou  2 , Pengxiang Guo  3 , Hua Bai  4 , Qifang Zhang  5   6
Affiliations

Lycorine induces apoptosis of acute myeloid leukemia cells and inhibits triglyceride production via binding and targeting FABP5

Xinming Liang et al. Ann Hematol. 2023 May.

Abstract

Acute myeloid leukemia (AML) is the most common hematopoietic malignancy with abnormal lipid metabolism. However, currently available information on the involvement of the alterations in lipid metabolism in AML development is limited. In this study, we demonstrate that FABP5 expression facilitates AML cell viability, protects AML cells from apoptosis, and maintains triglyceride production. Our bioinformatics analysis revealed that FABP5 expression was upregulated and correlated with unfavorable overall survival of AML patients. FABP5 expression may be used to distinguish normal and AML with high accuracy. FABP5-based risk score was an independent risk factor for AML patients. AML patients with highly expressed FABP5 predicted resistance to drugs. In vitro study showed that FABP5 expression was remarkably elevated in primary AML blasts and an AML cell line. Silencing FABP5 expression attenuated AML cell viability, reduced triglyceride production and lipid droplet accumulation, and induced apoptosis. We utilized AutoDock online tool to identify lycorine as an FABP5 inhibitor by binding FABP5 at amino acid residues Ile54, Thr56, Thr63, and Arg109. Lycorine treatment downregulated the expression levels of FABP5 and its target PPARγ, impaired AML cell viability, triggered apoptosis, and reduced triglyceride production in AML cells. These results demonstrate that FABP5 is critical for AML cell survival and highlight a novel metabolic vulnerability for AML.

Keywords: Acute myeloid leukemia; Apoptosis; Cell viability; FABP5; Lycorine; Triglyceride.

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