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脂联素及其对急性白血病细胞的影响:一种实验和生物信息学方法。

Adiponectin and Its Effects on Acute Leukemia Cells: An Experimental and Bioinformatics Approach.

机构信息

Naval Hospital of Athens, Department of Endocrinology Diabetes and Metabolism, Athens, Greece.

First Department of Dermatology and Venereology, "Andreas Syggros" Hospital National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Adv Exp Med Biol. 2021;1338:117-127. doi: 10.1007/978-3-030-78775-2_14.

DOI:10.1007/978-3-030-78775-2_14
PMID:34973016
Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. It is known that deregulation of adipokine pathways is probably implicated in the ontogenesis of ALL. The present work aims at investigating the role of adiponectin and its effects on an ALL cell line. The CCRF-CEM cells were used as a model. Cells have been treated with adiponectin, with different concentrations up to 72 h. Cytotoxicity and cell cycle distribution were investigated for all concentrations using flow cytometry. Selected concentrations were also used for additional microarray analysis, using a small gene set of cancer-related genes. Lower and higher adiponectin concentrations did not produce an inhibition of proliferation, as well as an increase in cell death. It was found that adiponectin regulated differentially genes, such as CD22, CDH1, IFNG, LCK, MSH2, SPINT2, and others. At the same time, it appeared that adiponectin-related gene expression was more active on chromosomes 18 and 1. Machine learning classification algorithms showed that several genes were grouped together indicating common regulatory mechanisms. The present study showed that adiponectin is able to induce gene differential expression in leukemic cells in vitro, suggesting a possible role in the progression of leukemia. It is also an indication that more studies are required in order to further understand the role of adiponectin and adipokines in general in the role of human neoplasms.

摘要

急性淋巴细胞白血病(ALL)是最常见的儿科恶性肿瘤。已知脂肪因子通路的失调可能与 ALL 的发生有关。本研究旨在探讨脂联素的作用及其对 ALL 细胞系的影响。使用 CCRF-CEM 细胞作为模型。用不同浓度的脂联素处理细胞,最高浓度达 72 小时。用流式细胞术检测所有浓度的细胞毒性和细胞周期分布。选择的浓度也用于使用与癌症相关的小基因集的额外微阵列分析。较低和较高的脂联素浓度不会抑制增殖,也不会增加细胞死亡。研究发现,脂联素调节了不同的基因,如 CD22、CDH1、IFNG、LCK、MSH2、SPINT2 等。同时,脂联素相关基因表达似乎在 18 号和 1 号染色体上更为活跃。机器学习分类算法表明,一些基因聚集在一起,表明存在共同的调节机制。本研究表明,脂联素能够在体外诱导白血病细胞的基因差异表达,提示其在白血病进展中可能发挥作用。这也表明,需要进一步研究以更好地了解脂联素和脂肪因子在人类肿瘤中的作用。

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脂联素、瘦素和胃饥饿素在儿童急性淋巴细胞白血病的进展和预后中的作用。
Leuk Lymphoma. 2019 Sep;60(9):2158-2169. doi: 10.1080/10428194.2019.1569230. Epub 2019 Jan 30.
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