论文标题：ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification

期刊： Frontiers of Medicine

作者：Wenle Ye, Jinghan Wang, Jiansong Huang, Xiao He, Zhixin Ma, Xia Li, Xin Huang, Fenglin Li, Shujuan Huang, Jiajia Pan, Jingrui Jin, Qing Ling, Yungui Wang, Yongping Yu, Jie Sun, Jie Jin

发表时间： 15 Aug 2023

DOI：10.1007/s11684-022-0942-1

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导 读

浙江大学医学院附属第一医院孙杰和金洁等在Frontiers of Medicine发表研究论文《ACSL5作为急性髓系白血病预后标志物通过棕榈酰化修饰调控Wnt/β-连环蛋白信号通路活性》（ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification）。本研究发现，ACSL5在急性髓系白血病（AML）患者中高表达且与不良预后相关，其通过促进Wnt3a蛋白的棕榈酰化修饰激活Wnt/β-连环蛋白信号通路驱动白血病细胞的增殖，而抑制ACSL5可协同ABT-199增强抗白血病效应，提示ACSL5可作为AML的预后标志物及治疗靶点。

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

酰基辅酶A合成酶长链家族成员5（ACSL5）属于酰基辅酶A合成酶（ACSs）家族，它通过催化脂酰辅酶A的合成来激活长链脂肪酸。ACSL5的异常调控已在胶质瘤和结肠癌等恶性肿瘤中被报道，但其在急性髓系白血病（AML）中的作用尚不明确。本研究发现，AML患者骨髓细胞中ACSL5的表达高于健康供体。ACSL5水平可作为AML患者总生存期的一个独立预后预测指标。在AML细胞中，敲低ACSL5可抑制体内及体外细胞的生长。从机制上讲，敲低ACSL5通过抑制Wnt3a的棕榈酰化修饰，进而抑制了Wnt/β-连环蛋白信号通路的激活。此外，泛ACS家族抑制剂triacsin c与美国食品药品监督管理局（FDA）批准的AML治疗药物BCL-2抑制剂ABT-199联合使用时，可协同抑制细胞生长并显著诱导细胞凋亡。以上结果表明，ACSL5是AML的潜在预后标志物，并为分子分型的AML提供了有前景的药物靶点。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification

作者

Wenle Ye^1,2, Jinghan Wang^1,2, Jiansong Huang^1,2, Xiao He³, Zhixin Ma⁴, Xia Li^1,2, Xin Huang^1,2, Fenglin Li^1,2, Shujuan Huang^1,2, Jiajia Pan^1,2, Jingrui Jin^1,2, Qing Ling^1,2, Yungui Wang^1,2, Yongping Yu⁵, Jie Sun^1,2, Jie Jin^1,2,6

机构

1. Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310003, China

2. Key Laboratory of Hematopoietic Malignancies, Diagnosis and Treatment, Hangzhou 310009, China

3. Research Centre, Centre hospitalier de lUniversité de Montréal (CRCHUM), Montreal, Quebec H2L 4M1, Canada

4. Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China

5. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

6. Cancer Center, Zhejiang University, Hangzhou 310058, China

通讯作者

Jie Sun, Jie Jin

引用这篇文章

Wenle Ye, Jinghan Wang, Jiansong Huang, Xiao He, Zhixin Ma, Xia Li, Xin Huang, Fenglin Li, Shujuan Huang, Jiajia Pan, Jingrui Jin, Qing Ling, Yungui Wang, Yongping Yu, Jie Sun, Jie Jin. ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification. Front. Med., 2023, 17(4): 685–698

https://doi.org/10.1007/s11684-022-0942-1

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-022-0942-1

https://link.springer.com/article/10.1007/s11684-022-0942-1

感谢作者对Frontiers of Medicine的信任和支持。

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