Jiang Xiandong, Huang Yingying, Hong Xiaoying, Wu Wei, Lin Yanfeng, Lin Liping, Xue Yan, Lin Donghong
Department of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, China.
Department of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Medical Technology Experimental Teaching Center, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China.
Transl Oncol. 2025 Feb;52:102227. doi: 10.1016/j.tranon.2024.102227. Epub 2024 Dec 6.
Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leukemia (AML). Here, we analyzed the relationship between lipid metabolism and ferroptosis in AML cells to explore new clinical treatment strategies. This study found that 12 fatty acids were significantly changed in acute myeloid leukemia cell ferroptosis, including dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA), etc. Exogenous DGLA substantially increases the sensitivity to ferroptosis and induces ferroptosis alone in AML cells. In addition, acyl-CoA synthetase long-chain family member 4 (ACSL4) knockout significantly inhibited DGLA-induced AML cells ferroptosis, and ACSL4 regulates DGLA-associated lipid synthesis to affect the sensitivity of AML cells to ferroptosis. Collectively, our studies indicate that a DGLA-enriched diet significantly restricted the growth of leukemia cells as well as induced ferroptosis in vivo.
铁死亡是一种由过量铁依赖性脂质过氧化引起的新型程序性细胞死亡。根据各项研究，铁死亡与脂质代谢之间可能存在联系。然而，关于急性髓系白血病（AML）中铁死亡的脂质代谢的报道较少。在此，我们分析了AML细胞中脂质代谢与铁死亡之间的关系，以探索新的临床治疗策略。本研究发现，急性髓系白血病细胞铁死亡中有12种脂肪酸发生了显著变化，包括二高-γ-亚麻酸（DGLA）、花生四烯酸（AA）、二十二碳六烯酸（DHA）等。外源性DGLA显著增加了对铁死亡的敏感性，并在AML细胞中单独诱导铁死亡。此外，酰基辅酶A合成酶长链家族成员4（ACSL4）基因敲除显著抑制了DGLA诱导的AML细胞铁死亡，且ACSL4调节与DGLA相关的脂质合成，以影响AML细胞对铁死亡的敏感性。总的来说，我们的研究表明，富含DGLA的饮食在体内显著限制了白血病细胞的生长并诱导了铁死亡。
