[骨髓成骨细胞通过上调白细胞介素-1促进白血病干细胞增殖]。

Zhi-Jie Cao, Yi-Shuang Li, Hui-Jun Wang, Zhen-Ya Xue, Shu-Ying Chen, Ke-Jing Tang, Min Wang, Qing Rao
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引用次数: 0

摘要

目的:探讨白血病细胞骨髓微环境的外源性调控机制,探讨成骨细胞生态位通过上调白血病细胞中白细胞介素-1 (IL-1)的表达对白血病干细胞增殖和自我更新的促进作用。方法:采用RNA测序和基因集富集分析(GSEA)方法检测AE9a小鼠骨髓内皮和中央骨髓白血病细胞的基因表达谱。采用实时荧光定量PCR (Quantitative real-time PCR, qRT-PCR)检测体外与成骨细胞共培养的AE9a小鼠白血病细胞中IL-1的表达。此外,我们还利用qRT-PCR检测了43例急性髓性白血病(AML)患者骨髓单核细胞(BMMNC)中IL-1的表达。白血病细胞与成骨细胞共培养或IL-1β处理后,采用集落形成实验测定AE9a白血病细胞的集落形成能力。结果:在AE9a白血病小鼠中,RNA-seq数据和GSEA显示,位于内皮的白血病细胞中富集的上调基因属于炎症反应基因集,其中IL-1α和IL-1β在位于成骨生态位的AE9a白血病细胞中表达显著升高(IL-1α: p2)。结论:成骨生态位可通过上调白血病细胞中IL-1的表达促进白血病细胞增殖和自我更新。在AML患者中,IL-1的表达水平与BMMNC中CD34阳性细胞的百分比相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Bone Marrow Osteoblasts Promotes the Proliferation Leukemia Stem Cell by Up-regulating Interleukin-1].

Objective: To explore the extrinsic regulation mechanism of bone marrow microenvironment in leukemia cells, and investigate the promoting effect of osteoblast niche on the proliferation and self-renewal of leukemia stem cell by up-regulating the expression of interleukin-1 (IL-1) in leukemia cell.

Methods: The gene expression profiles on leukemia cells derived from AE9a mouse bone marrow endosteum and central bone marrow were determined by RNA sequencing and gene set enrichment analysis (GSEA). Quantitative real-time PCR (qRT-PCR) was used to detect the expression of IL-1 in AE9a mouse leukemia cells co-cultured with or without osteoblasts in vitro. In addition, qRT-PCR was also used to determine the expression of IL-1 in bone marrow mononuclear cell (BMMNC) from 43 patients with acute myeloid leukemia (AML). For leukemia cells co-cultured with osteoblasts or treated with IL-1β, colony forming ability of AE9a leukemia cells was determined by colony formation assay.

Results: In AE9a leukemia mouse, RNA-seq data and GSEA showed that the enrichment of the upregulated genes in leukemia cells located in endosteum fell into inflammatory response gene set, among them, IL-1α and IL-1β were significantly higher expressed in AE9a leukemia cells that located osteoblast niche (IL-1α: P<0.001, IL-1β:P<0.001). After AE9a leukemia cells were co-cultured with osteoblasts in vitro, the expression of IL-1α and IL-1β in leukemia cells were increased by 2.5 and 3.5 times respectively. In colony formation assay, the number of colonies was increased significantly after leukemia cells were co-cultured with osteoblasts (P<0.001). In addition, when AE9a leukemia cells were treated with IL-1β, the number of colonies was also increased significantly (P<0.01). In AML patients, BMMNC with high percentage of CD34 positive cells exhibited higher level of IL-1 expression.

Conclusion: Osteoblast niche can promote leukemia cell proliferation and self-renewal through up-regulating the expression of IL-1 in leukemia cells. In AML patients, the expression level of IL-1 was correlated to the percentage of CD34 positive cells in BMMNC.

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