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多发性骨髓瘤患者治疗反应不同的造血龛间充质干细胞中基因的转录。

Transcription of Genes in Hematopoietic Niche's Mesenchymal Stem Cells in Multiple Myeloma Patients with Different Responses to Treatment.

机构信息

Russian Research Institute of Hematology and Transfusiology, FMBA of Russian Federation, 191024 St. Petersburg, Russia.

Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia.

出版信息

Genes (Basel). 2023 May 17;14(5):1097. doi: 10.3390/genes14051097.

Abstract

Mesenchymal stromal cells (MSCs) are involved in bone tissue remodeling due to their ability to differentiate into osteoblasts and to influence osteoclasts' activity. Multiple myeloma (MM) is associated with bone resorption. During disease progression, MSCs acquire a tumor-associated phenotype, losing their osteogenic potential. The process is associated with impaired osteoblasts/osteoclasts balance. The WNT signaling pathway plays a major role in maintaining the balance. In MM, it functions in an aberrant way. It is not known yet whether the WNT pathway is restored in patients' bone narrow after treatment. The aim of the study was to compare the level of family gene transcription in the bone marrow MSCs of healthy donors and MM patients before and after therapy. The study included healthy donors ( = 3), primary patients ( = 3) and patients with different response status to therapy (bortezomib-containing induction regimens) ( = 12). The transcription of the and (encoding β-catenin) genes was accessed using qPCR. The mRNA quantity of ten genes, as well as mRNA encoding β-catenin, a key mediator in canonical signaling, was evaluated. The observed differences between the groups of patients indicated that aberrant functioning of the WNT pathway was retained after treatment. The differences that we detected for , and suggested their possible application as prognostic molecular markers.

摘要

间充质基质细胞(MSCs)能够分化为成骨细胞并影响破骨细胞的活性,从而参与骨组织重塑。多发性骨髓瘤(MM)与骨吸收有关。在疾病进展过程中,MSCs 获得肿瘤相关表型,丧失成骨潜能。这一过程与成骨细胞/破骨细胞平衡受损有关。WNT 信号通路在维持平衡中起主要作用。在 MM 中,它以异常的方式发挥作用。目前尚不清楚患者在治疗后骨髓中的 WNT 途径是否恢复。本研究旨在比较健康供体和 MM 患者治疗前后骨髓间充质基质细胞中家族基因转录的水平。该研究包括健康供体(n = 3)、初诊患者(n = 3)和对不同治疗反应状态的患者(硼替佐米联合诱导方案)(n = 12)。使用 qPCR 检测 和 (编码β-catenin)基因的转录。评估了十个 基因的 mRNA 量,以及作为经典信号传导关键介质的β-catenin 的 mRNA。患者组之间观察到的差异表明,WNT 途径的异常功能在治疗后仍然存在。我们检测到 、 和 之间的差异表明它们可能作为预后分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32b1/10218155/5e14ab51f697/genes-14-01097-g001.jpg

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