半乳糖凝集素-1:髓细胞分化和急性髓细胞白血病的重要调节因子,是一种有前景的预后指标和治疗靶点

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Lulu Liu , Panpan Cheng , Junjie Cui , Saisai Ren , Mingkang Yao , Ling Li , Hui Zhou , Xianning Zhang , Xianyun Qin , Yaqi Liu , Hao Zhang , Lina Wang , Mingtai Chen
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引用次数: 0

摘要

急性髓性白血病(AML)是一种侵袭性和异质性的血液系统恶性肿瘤,生存率低,治疗选择有限。尽管半乳糖凝集素-1 (LGALS1)与实体瘤的肿瘤细胞存活和免疫逃避有关,但其在AML中的作用尚不清楚。在本研究中,我们发现与对照样本相比,AML患者的LGALS1在mRNA和蛋白水平上均表现出明显的上调。生物信息学分析表明,LGALS1的高表达是AML患者总体生存的重要不利预后因素,与不良的临床和遗传特征以及免疫细胞浸润相关。AML细胞中LGALS1的缺失会阻碍细胞增殖,诱导细胞凋亡并促进髓细胞分化。使用LGALS1抑制剂OTX008治疗可显著降低AML患者原发性恶性骨髓细胞的活力。值得注意的是,治疗后AML-M5患者中LGALS1的表达明显降低,这可能是由于其在AML-M5亚型中的表达高于其他FAB亚型。综上所述,我们的研究结果表明LGALS1可以作为AML的独立预后危险因素和有希望的治疗靶点,为AML的发病机制提供了新的见解,并为开发新的治疗策略奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Galectin-1: An important regulator in myeloid differentiation and acute myeloid leukemia as well as a promising prognostic indicator and therapeutic target
Acute myeloid leukemia (AML) is an aggressive and heterogeneous hematological malignancy with a low survival probability and limited therapeutic options. Although galectin-1 (LGALS1) has been implicated in tumor cell survival and immune evasion in solid tumor, its role in AML is still unclear. In this study, we found that LGALS1 presents prominent upregulation in AML patients at both mRNA and protein levels compared with the control samples. Bioinformatics analysis indicated that high expression of LGALS1 is a significant unfavorable prognostic factor for overall survival in AML, correlating with adverse clinical and genetic features as well as immune cell infiltration. Depletion of LGALS1 in AML cells impeded cell proliferation, induced apoptosis and promoted myeloid differentiation. Treatment with OTX008, an LGALS1 inhibitor, markedly diminished the viability of primary malignant bone marrow cells from AML patients. Notably, LGALS1 expression was significantly reduced exclusively in AML-M5 patients after treatment, which may be due to its higher expression in AML-M5 subtype compared to other FAB subtypes. In summary, our findings indicate that LGALS1 could serve as an independent prognostic risk factor and a promising therapeutic target in AML, providing novel insights into AML pathogenesis and laying the foundation for the development of new therapeutic strategies.
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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