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三种主要类型白血病中烟碱型α7亚型和毒蕈碱型M3亚型乙酰胆碱受体表达的变化

Variation of nicotinic subtype α7 and muscarinic subtype M3 acetylcholine receptor expression in three main types of leukemia.

作者信息

Suriyo Tawit, Chotirat Sadudee, Auewarakul Chirayu U, Chaiyot Karnjana, Promsuwicha Orathai, Satayavivad Jutamaad

机构信息

Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok 10210, Thailand.

Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok 10400, Thailand.

出版信息

Oncol Lett. 2019 Jan;17(1):1357-1362. doi: 10.3892/ol.2018.9663. Epub 2018 Nov 5.

DOI:10.3892/ol.2018.9663
PMID:30655906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6313006/
Abstract

Cholinergic receptors, such as α7-nicotinic acetylcholine receptor (α7-nAChR) and M3-muscarinic acetylcholine receptor (M3-mAChR), have been demonstrated to serve a significant role in the proliferation, differentiation and apoptosis of leukemic cells. However, the expression of these receptors in samples from patients with leukemia remains unclear. The present study aimed to determine the expression of M3-mAChR and α7-nAChR in the bone marrow or peripheral blood of 51 patients with leukemia, including acute myeloid leukemia (AML; n=33), acute lymphoblastic leukemia (ALL; n=13), and chronic myeloid leukemia (CML; n=5). Peripheral blood mononuclear cells (PBMCs) were also isolated from healthy subjects (n=5) for comparison. Western blot analysis was performed to determine the protein expression profiles, and a pattern of decreased α7-nAChR levels in patients with leukemia was observed. Among the leukemia types, the lowest expression of α7-nAChR and M3-mAChR were identified in patients with T-cell ALL/lymphoma (T-ALL). CML exhibited the highest level of M3-mAChR, which was significantly different from APL and AML-M4, yet not from healthy subjects (P<0.05). Therefore, different expression profiles of α7-nACR and M3-mAChR were detected amongst the leukemia types. Collectively, the present study supports the potential role of cholinergic signaling in mediating leukemogenesis. However, further studies in larger cohorts are required to validate these findings.

摘要

胆碱能受体,如α7-烟碱型乙酰胆碱受体(α7-nAChR)和M3-毒蕈碱型乙酰胆碱受体(M3-mAChR),已被证明在白血病细胞的增殖、分化和凋亡中发挥重要作用。然而,这些受体在白血病患者样本中的表达仍不清楚。本研究旨在确定51例白血病患者骨髓或外周血中M3-mAChR和α7-nAChR的表达,其中包括急性髓系白血病(AML;n = 33)、急性淋巴细胞白血病(ALL;n = 13)和慢性髓系白血病(CML;n = 5)。还从健康受试者(n = 5)中分离外周血单个核细胞(PBMC)用于比较。进行蛋白质印迹分析以确定蛋白质表达谱,观察到白血病患者中α7-nAChR水平降低的模式。在白血病类型中,T细胞ALL/淋巴瘤(T-ALL)患者中α7-nAChR和M3-mAChR的表达最低。CML的M3-mAChR水平最高,与急性早幼粒细胞白血病(APL)和AML-M4有显著差异,但与健康受试者无显著差异(P<0.05)。因此,在不同白血病类型中检测到α7-nACR和M3-mAChR的不同表达谱。总体而言,本研究支持胆碱能信号在介导白血病发生中的潜在作用。然而,需要在更大队列中进行进一步研究以验证这些发现。

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本文引用的文献

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A review of risk factors for childhood leukemia.儿童白血病危险因素综述。
Eur Rev Med Pharmacol Sci. 2016 Sep;20(18):3760-3764.
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Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.胆碱能机制作为急性淋巴细胞性T白血病的相关靶点
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