Haematologica:研究发现TGFβ1是引起骨髓增生异常综合征和急性髓系白血病间充质干细胞的功能性抑制触发因子

2018-06-24 MedSci MedSci原创

间充质基质细胞参与骨髓增生异常综合征和急性髓细胞白血病的发病机制,但其潜在机制尚不完全清楚。为了进一步表征病理学表型,我们对来自骨髓增生异常综合征和急性骨髓性白血病患者的间充质基质细胞进行了RNA测序,揭示了通常在骨髓增生异常综合征和急性骨髓性白血病中表达异常的基因的特定分子标记。通路分析显示,与骨生成、衰老、炎症和抑制性细胞因子有关的基因的强烈富集,从而在分子水平上反映骨髓增生异常综合征和急性髓

间充质基质细胞参与骨髓增生异常综合征和急性髓细胞白血病的发病机制,但其潜在机制尚不完全清楚。为了进一步表征病理学表型,我们对来自骨髓增生异常综合征和急性骨髓性白血病患者的间充质基质细胞进行了RNA测序,揭示了通常在骨髓增生异常综合征和急性骨髓性白血病中表达异常的基因的特定分子标记。

通路分析显示,与骨生成、衰老、炎症和抑制性细胞因子有关的基因的强烈富集,从而在分子水平上反映骨髓增生异常综合征和急性髓性白血病中间质基质细胞的结构和功能缺陷。进一步分析确定TGFβ1是这种异常表达基因最可能的外在触发因子。

在暴露于TGFβ1之后,健康的间充质基质细胞出现功能缺陷和表现型与患者衍生的基质细胞中观察到的表型相同。 TGF-β1对基质细胞功能的这些抑制作用被已确定的TGFβ受体信号传导抑制剂SD-208所抵消。通过SD-208阻断TGFβ信号还恢复了患者来源的基质细胞的成骨分化能力,从而证实了TGFβ1在患有骨髓增生异常综合征和急性髓性白血病的患者的骨髓微环境中的作用。

综上所述,该研究结果建立了TGFβ1作为引起骨髓增生异常综合征和急性髓细胞性白血病中MSC的功能性抑制的相关触发因子,并鉴定SD-208为恢复这些效应的候选者。

原始出处:

Geyh S, Rodríguez-Paredes M, et al., TGFβ1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia. Haematologica. 2018 May 17. pii: haematol.2017.186734. doi: 10.3324/haematol.2017.186734. 

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time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1821760, encodeId=e35a1821e60f6, content=<a href='/topic/show?id=d1ba10196122' target=_blank style='color:#2F92EE;'>#骨髓增生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101961, encryptionId=d1ba10196122, topicName=骨髓增生)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=fengyqf, createdTime=Sun Oct 14 02:17:00 CST 2018, time=2018-10-14, status=1, ipAttribution=)]
    2018-09-27 changhe713
  5. 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time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1821760, encodeId=e35a1821e60f6, content=<a href='/topic/show?id=d1ba10196122' target=_blank style='color:#2F92EE;'>#骨髓增生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101961, encryptionId=d1ba10196122, topicName=骨髓增生)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=fengyqf, createdTime=Sun Oct 14 02:17:00 CST 2018, time=2018-10-14, status=1, ipAttribution=)]
    2018-07-28 yuanming7
  6. 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time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1821760, encodeId=e35a1821e60f6, content=<a href='/topic/show?id=d1ba10196122' target=_blank style='color:#2F92EE;'>#骨髓增生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101961, encryptionId=d1ba10196122, topicName=骨髓增生)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=fengyqf, createdTime=Sun Oct 14 02:17:00 CST 2018, time=2018-10-14, status=1, ipAttribution=)]
  7. 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time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1821760, encodeId=e35a1821e60f6, content=<a href='/topic/show?id=d1ba10196122' target=_blank style='color:#2F92EE;'>#骨髓增生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101961, encryptionId=d1ba10196122, topicName=骨髓增生)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=fengyqf, createdTime=Sun Oct 14 02:17:00 CST 2018, time=2018-10-14, status=1, ipAttribution=)]
    2019-03-26 changfy
  8. 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time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1821760, encodeId=e35a1821e60f6, content=<a href='/topic/show?id=d1ba10196122' target=_blank style='color:#2F92EE;'>#骨髓增生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101961, encryptionId=d1ba10196122, topicName=骨髓增生)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=fengyqf, createdTime=Sun Oct 14 02:17:00 CST 2018, time=2018-10-14, status=1, ipAttribution=)]
    2019-05-27 yangeasy
  10. 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