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血清素受体 1B(HTR1B)mRNA 表达增加与 BCR::ABL1 阴性骨髓增殖性肿瘤中的血栓形成有关。

Increased mRNA expression for serotonin receptor 1B (HTR1B) is associated with thrombosis in BCR::ABL1-negative myeloproliferative neoplasms.

机构信息

Cellular and Molecular Pathology Department, Stefan S. Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania.

Cytogenomic Medical Laboratory, Bucharest, Romania.

出版信息

J Cell Mol Med. 2024 Aug;28(16):e70024. doi: 10.1111/jcmm.70024.

DOI:10.1111/jcmm.70024
PMID:39183370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11345121/
Abstract

BCR

:ABL1-negative myeloproliferative neoplasms (MPNs) are clonal haematopoietic stem cell disorders characterized by specific driver mutations and an increased risk of both macrothrombosis and microthrombosis. Serotonin receptor type 1B (HTR1B) was found to be expressed by various solid tumours, and also primary bone marrow mononuclear cells from myelodysplastic neoplasm and acute myeloid leukaemia patients, representing a potential therapeutic target. In this study we assessed for the first time the expression levels of HTR1B mRNA in the peripheral blood mononuclear cells (PBMC) of 85 newly diagnosed MPN patients, consisting of 28 polycythemia vera, 25 essential thrombocythemia and 32 primary myelofibrosis cases. Levels of HTR1B expression between MPN subtypes and control group were not significantly different. However, at clinical data examination, it was observed that MPN patients with a recent history of major thrombosis and/or signs of impaired microcirculation exhibited significantly higher HTR1B expression levels compared to non-thrombotic MPNs and control group. Moreover, thrombotic MPN patients had significantly higher HTR1B expression than patients with recent thrombosis and absence of MPN diagnostic criteria. These findings suggest that increased levels of HTR1B expression in PBMC might be associated with thrombosis in MPN patients, but larger studies are needed for confirmation, including testing of the receptor protein expression level.

摘要

BCR

:ABL1 阴性骨髓增殖性肿瘤(MPN)是一种克隆性造血干细胞疾病,其特征为特定的驱动突变,并增加了巨血栓和微血栓形成的风险。发现 5-羟色胺受体 1B(HTR1B)在各种实体瘤中表达,也在骨髓增生异常和急性髓系白血病患者的原始骨髓单核细胞中表达,代表了一个潜在的治疗靶点。在这项研究中,我们首次评估了 85 名新诊断的 MPN 患者外周血单核细胞(PBMC)中 HTR1B mRNA 的表达水平,包括 28 例真性红细胞增多症、25 例原发性血小板增多症和 32 例原发性骨髓纤维化病例。MPN 亚型与对照组之间的 HTR1B 表达水平没有显著差异。然而,在临床数据分析中,我们观察到近期有重大血栓形成史和/或微循环受损迹象的 MPN 患者与非血栓性 MPN 和对照组相比,HTR1B 表达水平显著升高。此外,血栓性 MPN 患者的 HTR1B 表达水平明显高于近期有血栓形成且无 MPN 诊断标准的患者。这些发现表明,PBMC 中 HTR1B 表达水平的升高可能与 MPN 患者的血栓形成有关,但需要更大规模的研究来证实,包括受体蛋白表达水平的检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c7d/11345121/58f4d77a37ea/JCMM-28-e70024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c7d/11345121/a11c7ef3f990/JCMM-28-e70024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c7d/11345121/58f4d77a37ea/JCMM-28-e70024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c7d/11345121/a11c7ef3f990/JCMM-28-e70024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c7d/11345121/58f4d77a37ea/JCMM-28-e70024-g001.jpg

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本文引用的文献

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The discovery, structure, and function of 5-HTR1E serotonin receptor.5-HTR1E 血清素受体的发现、结构与功能。
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Thromboinflammation in Myeloproliferative Neoplasms (MPN)-A Puzzle Still to Be Solved.骨髓增殖性肿瘤(MPN)中的血栓炎症——一个待解决的难题。
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JAK2V617F variant allele frequency >50% identifies patients with polycythemia vera at high risk for venous thrombosis.JAK2V617F 等位基因变异频率>50%可识别出患有静脉血栓形成高风险的真性红细胞增多症患者。
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Still a burning question: the interplay between inflammation and fibrosis in myeloproliferative neoplasms.仍然是一个悬而未决的问题:炎症和纤维化在骨髓增殖性肿瘤中的相互作用。
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The pathobiology of thrombosis, microvascular disease, and hemorrhage in the myeloproliferative neoplasms.骨髓增殖性肿瘤中的血栓形成、微血管病和出血的病理生物学。
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