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Blood:CML幼稚细胞通过BMP自分泌环来逃逸TKI治疗。

2017-11-15 MedSci MedSci原创

BCR-ABL特异性的酪氨酸酶抑制剂(TKI)可影响慢性粒细胞白血病(CML)患者的预后,使危及生命的疾病转为慢性病。但是,TKI并不是十分有效,因为多数患者的骨髓内仍有白血病干细胞(LSC)及其祖细胞残留,治疗终止后可复发。

中心点:

TKI耐药的CML患者的白血病幼稚细胞及其niche表现出顽固性的BMP信号通路异常。

一个TKI耐受的白血病干细胞的亚型通过将BMP4与BMPR1b结合来保护TWIST-1表达细胞而存活。

摘要:

BCR-ABL特异性的酪氨酸酶抑制剂(TKI)可影响慢性粒细胞白血病(CML)患者的预后,使危及生命的疾病转为慢性病。但是,TKI并不是十分有效,因为多数患者的骨髓内仍有白血病干细胞(LSC)及其祖细胞残留,治疗终止后可复发。

骨髓形态蛋白(BMP)通路异常参与LSC及其祖细胞的扩增。在本篇报道中,作者发现在TKI耐受性的患者中,BMP通路异常持续存在。与完全细胞遗传缓解(CCyR)的患者相比,TKI耐药的LSC/祖细胞表现出BMPR1b高表达,且其细胞定位发生改变。

在体外,单用TKI或联合IFN-α处理慢性期(CP)的幼稚CML细胞,发现BMPR1b+的细胞存活率最高。研究人员证实可通过耐药患者的间充质细胞持续增加BMP4的表达。患者的随访结果显示,与诊断时相比,TKI耐药性患者的BMPR1b的表达量增加,其LSC的BMP4的表达量也增加,但在敏感性患者中没有改变。

在TKI耐药性患者的骨髓中,白血病细胞和非白血病细胞均表现为BMP4高表达。暴露于BMP2/BMP4不影响BCR-ABL的转录,但会伴随TWIST-1(在耐药性LSC中高表达的一个转录因子)的过表达。通过调节BMP4或BMPR1b的表达量,研究人员证明上述元件参与TKI耐药机制。

综上所述,Elodie Grockowiak等人证明了BMP的持续异常和一个自分泌环的存在促进CML原始细胞产生TKI耐药性。

原始出处:

Elodie Grockowiak, et al.Immature CML cells Implement a BMP Autocrine Loop to Escape TKI Treatment.Blood  2017  :blood-2017-08-801019;  doi: https://doi.org/10.1182/blood-2017-08-801019

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    2017-12-19 HNYYM
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    2018-01-23 gwc392
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    2017-11-18 大爰

    学习并分享!!

    0

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    2017-11-17 lsj628
  5. [GetPortalCommentsPageByObjectIdResponse(id=1634011, encodeId=212916340119a, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d95322064897, createdName=HNYYM, createdTime=Tue Dec 19 18:48:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682374, encodeId=dec816823e403, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Jan 23 04:48:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262222, encodeId=8d9426222270, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Nov 18 09:26:37 CST 2017, time=2017-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384180, encodeId=1e8013841803a, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488702, encodeId=e83e1488e020e, content=<a href='/topic/show?id=20b24899a7' target=_blank style='color:#2F92EE;'>#CML#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4899, encryptionId=20b24899a7, topicName=CML)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b3e8470831, createdName=wangbingxhy, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261828, encodeId=bd6126182862, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Thu Nov 16 23:08:49 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261619, encodeId=25af261619d8, content=谢谢分享.阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Nov 16 07:01:01 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261555, encodeId=948b26155586, content=学习了不少事情!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K4BGdu4COj6QWFqgMd3xnWDdgLZKUGI32veZvO2qFAQvpYr1eMbUOTqMvlZWc3MsugtFMHzxDwial/0, createdBy=88731939304, createdName=圣艮山, createdTime=Wed Nov 15 22:15:10 CST 2017, time=2017-11-15, status=1, ipAttribution=)]
    2017-11-17 wangbingxhy
  6. [GetPortalCommentsPageByObjectIdResponse(id=1634011, encodeId=212916340119a, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d95322064897, createdName=HNYYM, createdTime=Tue Dec 19 18:48:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682374, encodeId=dec816823e403, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Jan 23 04:48:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262222, encodeId=8d9426222270, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Nov 18 09:26:37 CST 2017, time=2017-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384180, encodeId=1e8013841803a, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488702, encodeId=e83e1488e020e, content=<a href='/topic/show?id=20b24899a7' target=_blank style='color:#2F92EE;'>#CML#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4899, encryptionId=20b24899a7, topicName=CML)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b3e8470831, createdName=wangbingxhy, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261828, encodeId=bd6126182862, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Thu Nov 16 23:08:49 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261619, encodeId=25af261619d8, content=谢谢分享.阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Nov 16 07:01:01 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261555, encodeId=948b26155586, content=学习了不少事情!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K4BGdu4COj6QWFqgMd3xnWDdgLZKUGI32veZvO2qFAQvpYr1eMbUOTqMvlZWc3MsugtFMHzxDwial/0, createdBy=88731939304, createdName=圣艮山, createdTime=Wed Nov 15 22:15:10 CST 2017, time=2017-11-15, status=1, ipAttribution=)]
    2017-11-16 1e1b8538m79(暂无匿称)

    不错的文章值得推荐

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1634011, encodeId=212916340119a, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d95322064897, createdName=HNYYM, createdTime=Tue Dec 19 18:48:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682374, encodeId=dec816823e403, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Jan 23 04:48:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262222, encodeId=8d9426222270, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Nov 18 09:26:37 CST 2017, time=2017-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384180, encodeId=1e8013841803a, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488702, encodeId=e83e1488e020e, content=<a href='/topic/show?id=20b24899a7' target=_blank style='color:#2F92EE;'>#CML#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4899, encryptionId=20b24899a7, topicName=CML)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b3e8470831, createdName=wangbingxhy, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261828, encodeId=bd6126182862, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Thu Nov 16 23:08:49 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261619, encodeId=25af261619d8, content=谢谢分享.阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Nov 16 07:01:01 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261555, encodeId=948b26155586, content=学习了不少事情!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K4BGdu4COj6QWFqgMd3xnWDdgLZKUGI32veZvO2qFAQvpYr1eMbUOTqMvlZWc3MsugtFMHzxDwial/0, createdBy=88731939304, createdName=圣艮山, createdTime=Wed Nov 15 22:15:10 CST 2017, time=2017-11-15, status=1, ipAttribution=)]
    2017-11-16 刘煜

    谢谢分享.阅读

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1634011, encodeId=212916340119a, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d95322064897, createdName=HNYYM, createdTime=Tue Dec 19 18:48:00 CST 2017, time=2017-12-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682374, encodeId=dec816823e403, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Tue Jan 23 04:48:00 CST 2018, time=2018-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=262222, encodeId=8d9426222270, content=学习并分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Sat Nov 18 09:26:37 CST 2017, time=2017-11-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384180, encodeId=1e8013841803a, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488702, encodeId=e83e1488e020e, content=<a href='/topic/show?id=20b24899a7' target=_blank style='color:#2F92EE;'>#CML#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4899, encryptionId=20b24899a7, topicName=CML)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8b3e8470831, createdName=wangbingxhy, createdTime=Fri Nov 17 12:48:00 CST 2017, time=2017-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261828, encodeId=bd6126182862, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Thu Nov 16 23:08:49 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261619, encodeId=25af261619d8, content=谢谢分享.阅读, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Nov 16 07:01:01 CST 2017, time=2017-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261555, encodeId=948b26155586, content=学习了不少事情!, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K4BGdu4COj6QWFqgMd3xnWDdgLZKUGI32veZvO2qFAQvpYr1eMbUOTqMvlZWc3MsugtFMHzxDwial/0, createdBy=88731939304, createdName=圣艮山, createdTime=Wed Nov 15 22:15:10 CST 2017, time=2017-11-15, status=1, ipAttribution=)]
    2017-11-15 圣艮山

    学习了不少事情!

    0

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