Stem cells:JAK2V617F突变型巨核细胞可通过促血小板生成素/MPL信号促进造血干/祖细胞扩增

2018-08-02 MedSci MedSci原创

骨髓增生性肿瘤(MPNs)是以造血干细胞/祖细胞(HSPC)扩增和成熟血细胞过度产生为特征的干细胞疾病。获得性激酶突变JAK2V617F在这类疾病中发挥重要作用。HSPC在MPNs中的扩增机制尚未完全明确,限制了治疗措施的疗效。MPNs患者的一个显著特征是巨核细胞(MK)增生。zhangyu等人既往发现JAK2V617F突变型MKs可导致小鼠罹患骨髓增生异常综合征,伴随HSPC扩增。现其再次发现J

骨髓增生性肿瘤(MPNs)是以造血干细胞/祖细胞(HSPC)扩增和成熟血细胞过度产生为特征的干细胞疾病。获得性激酶突变JAK2V617F在这类疾病中发挥重要作用。HSPC在MPNs中的扩增机制尚未完全明确,限制了治疗措施的疗效。

MPNs患者的一个显著特征是巨核细胞(MK)增生。zhangyu等人既往发现JAK2V617F突变型MKs可导致小鼠罹患骨髓增生异常综合征,伴随HSPC扩增。现其再次发现JAK2V617F突变型MKs可通过诱导HSPC静止,增强MPN干细胞功能。

此外,研究人员还发现促血小板生成素及其受体MPL既可直接影响MKs的数量和质量,又可改变MK-内皮细胞的相互作用和血管壁龛功能,对JAK2V617F突变型MK诱导的骨髓增生至关重要。

因此,靶向HSPC壁龛-形成MKs和/或其在血管壁龛中的相互作用,或许可为MPNs患者提供新的更有效的治疗措施。

原始出处:

Yu Zhang, Chi Hua Sarah Lin,et al. JAK2V617F Megakaryocytes Promote Hematopoietic Stem/Progenitor Cell Expansion in Mice Through Thrombopoietin/MPL Signaling. Stem cells. July 13,2018.https://doi.org/10.1002/stem.2888

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    2019-06-21 仁者大医
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    2019-02-27 xuyong536
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  5. 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  6. 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time=2018-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615014, encodeId=0130161501434, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Sat Aug 04 02:33:00 CST 2018, time=2018-08-04, status=1, ipAttribution=)]
    2019-03-17 维他命
  8. 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time=2018-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615014, encodeId=0130161501434, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Sat Aug 04 02:33:00 CST 2018, time=2018-08-04, status=1, ipAttribution=)]
    2018-08-04 ylzr123

    好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!

    0

  9. 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time=2018-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615014, encodeId=0130161501434, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Sat Aug 04 02:33:00 CST 2018, time=2018-08-04, status=1, ipAttribution=)]
    2018-08-04 俅侠
  10. 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中心点:小鼠ADAP缺陷可导致血小板寿命缩短和异位释放,进而导致微血小板减少。巨核细胞缺乏ADAP会损坏DMS极化和伪足小体形成。摘要:骨髓巨核细胞(MKs)通过将血小板前体延伸到窦状血管产生血小板。血小板生成缺陷可导致血小板减少症,增加出血倾向。近期,有报道称先天性常染色体隐性小血小板减少症(CARST)是由ADAP(黏附和脱颗粒促进调节蛋白,又名FYB、SLAP130/120)基因突变导致的,

先天性巨核细胞增生不良性血小板减少症的研究进展

先天性巨核细胞增生不良性血小板减少症(CAMT)是一种罕见的遗传性骨髓衰竭综合征,表现为严重的血小板减少、骨髓巨核细胞减少或缺如,不伴有特异性躯体畸形,最终发展为再生障碍性贫血或继发性骨髓恶性肿瘤。在早期报道中,由于无法及时进行血小板输注及造血干细胞移植(HSCT)等相关治疗,多数患儿最终发展为骨髓衰竭而死亡。近年来随着对该病发病机制的深入研究及HSCT的广泛开展,许多患儿已得到成功救治。国内关于

Blood:敲除CK2β基因可以减少血栓形成,甚至可降低中风风险。

血小板,巨核细胞分裂出的无核细胞质,在止血和动脉血栓形成过程中发挥重要作用。酪蛋白激酶2(CK2)在巨核细胞和血小板中都可以检测到,对于CK2依赖性信号通路对巨噬细胞/血小板的病理生理机制的作用尚不明确。

Nat Med:巨核细胞可控制造血干细胞 有望治疗多种疾病

巨核细胞被认为是产生血小板愈合伤口最好的细胞,这些在骨髓中发现的巨大细胞在调节干细胞上也扮演着重要的角色,这是近日来自美国密苏里州斯托瓦斯医学研究所(Stowers Institute for Medical Research)的研究人员的一项重大研究发现,相关研究成果刊登于国际杂志Nature Medicine上。 实际上,造血干细胞在骨髓中可以分化形成巨核细胞,而本文研究者也首次发现造血