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酪氨酸激酶抑制剂停药相关肌肉骨骼疼痛的慢性粒细胞白血病患者中外泌体miRNA-140-3p上调。

Up-regulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors.

作者信息

Asano Michiyo, Umezu Tomohiro, Katagiri Seiichiro, Kobayashi Chiaki, Tauchi Tetsuzo, Gotoh Moritaka, Ando Keiko, Okabe Seiichi, Ohyashiki Junko H, Ohyashiki Kazuma

机构信息

Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.

Department of Hematology, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.

出版信息

Int J Hematol. 2017 Apr;105(4):419-422. doi: 10.1007/s12185-017-2199-z. Epub 2017 Feb 14.

DOI:10.1007/s12185-017-2199-z
PMID:28197964
Abstract

We analyzed the exosomal miRNA from peripheral blood from CML patients with musculoskeletal pain after stopping tyrosine kinase inhibitors to identify possible factors related to this manifestation. Exosomal miRNA profiling using TaqMan low-density array revealed that exosomal miR-140-3p was significantly elevated in CML patients showing musculoskeletal pain, when compared to those without such pain (P = 0.0336) or healthy individuals (P = 0.0022). All five CML patients with musculoskeletal pain and increased exosomal miR-140-3p levels sustained deep molecular responses: four of them achieved symptom relief and a significant decrease in exosomal miR-140-3p levels was evident. Because exosomal miR-140-3p is considered to have an inflammation-associated biological function in airway smooth muscle cells and targets Myomarker muscle-specific transmembrane protein, it appears that its overexpression in circulating exosomal miR-140-3p may have some role in the mechanism underlying self-limited musculoskeletal pain.

摘要

我们分析了慢性髓性白血病(CML)患者在停用酪氨酸激酶抑制剂后出现肌肉骨骼疼痛的外周血中的外泌体 miRNA,以确定与这种表现相关的可能因素。使用 TaqMan 低密度阵列进行外泌体 miRNA 谱分析显示,与无肌肉骨骼疼痛的 CML 患者(P = 0.0336)或健康个体(P = 0.0022)相比,出现肌肉骨骼疼痛的 CML 患者中外泌体 miR-140-3p 显著升高。所有 5 例有肌肉骨骼疼痛且外泌体 miR-140-3p 水平升高的 CML 患者均维持深度分子反应:其中 4 例症状缓解,外泌体 miR-140-3p 水平明显下降。由于外泌体 miR-140-3p 被认为在气道平滑肌细胞中具有与炎症相关的生物学功能,并且靶向 Myomarker 肌肉特异性跨膜蛋白,因此循环外泌体 miR-140-3p 的过表达似乎在自限性肌肉骨骼疼痛的潜在机制中发挥了一定作用。

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