Cell Stem Cell：白血病无需骨髓移植就能治愈？核心机制被发现！

2018-05-30 Paris,Zoe 转化医学网

那如何有效地控制造血干细胞的衰老呢？维也纳医科大学的合资企业Max F. Perutz实验室的Manuela Baccarini小组对细胞内信号如何保护激活和休眠之间的微妙平衡进行了研究，他们的研究结果发表在著名杂志《Cell Stem Cell》上。

导读

全世界每年有大量的人死于白血病，仅仅依靠骨髓移植来治疗白血病，效果却也只是杯水车薪而已。大部分白血病，特别是急性髓系白血病及慢性髓系白血病的发生，都直接或间接与造血干细胞异常相关，它在机体的整个生命过程中维持造血功能。临床上进行骨髓移植时，HSC（造血干细胞）的数量和功能是影响治疗效果的关键。而受多种因素的影响，机体内的造血干细胞大多会衰老，这不仅会影响治疗效果，甚至造成患者死亡。

那如何有效地控制造血干细胞的衰老呢？维也纳医科大学的合资企业Max F. Perutz实验室的Manuela Baccarini小组对细胞内信号如何保护激活和休眠之间的微妙平衡进行了研究，他们的研究结果发表在著名杂志《Cell Stem Cell》上。

为了弥补失血，通常处于休眠状态的造血干细胞（HSC）开始主动自我更新并分化成所有血细胞类型。但在完成任务后，HSC需要非常迅速地恢复到休眠状态，从而避免衰竭，这需要非常微妙的平衡。激活或休眠的倾向会对生物体造成灾难性后果，在最坏的情况下甚至导造成死亡。

MFPL的Manuela Baccarini小组发现了这种微妙平衡背后的机制。第一作者克里斯蒂安·鲍姆加特纳（Christian Baumgartner）澄清道：“到目前为止，我们知道激活和恢复休眠之间的平衡存在并且是必不可少的，但不是如何保持和参与哪些球员。”新的论文确定了参与者，并详细说明了它们在压力诱导下，血液生产过程中的监管。

Manuela Baccarini说：“两个关键的细胞内信号通路，几乎总是被平行激活，通过一个反馈回路协调，使HSCs保持完美平衡。其优点在于系统将被重置，而不管启动它的刺激是什么”。为了证明这一点，该小组故意从反馈回路中移除其中一名参与者，发现整个平衡发生了变化，造成HSC活动不受限制，HSC室被耗尽，最终未能产生足够的血细胞来补偿亏损。

接下来，Baccarini及其同事确定了一种细胞内源反馈机制，限制造血干细胞在激活过程中MEK / ERK和AKT / mTORC1信号的强度。该机制取决于激活的ERK对MEK1的负反馈磷酸化，这是防止HSC耗尽所必需的。而他们的研究也取得了预期的结果：开发用于癌症治疗的MEK抑制剂可能在控制HSC活化中具有额外的效用。有效的造血功能需要MEK / ERK和PI3K通路的微调。

骨髓移植

调节造血作用的信号的复杂性限制了旨在调节HSCs进入或退出静止的干预措施的设计，而这里描述的反馈机制是可药用的，这表明针对MEK / ERK通路可以发展为一种策略，以优化HSC区室，根据假设，靶向MEK / ERK以调节两种途径可以促进恶性干细胞从静止状态退出以使其敏感化疗和/或刺激其分化。目前，科学家们正努力将这种策略向临床试验发展，如果顺利，或许在不久的将来，治疗白血病的“神药”就会上市。

原始出处：

ChristianBaumgartner, StefanieToifl, MatthiasFarlik,et al. Christian Baumgarther，Stefanie Toifl An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion. Cell Stem Cell. 24 May 2018

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2019-04-04 circumcision

#核心机制#

42 0
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2018-06-24 hb2008ye

#stem cell#

32 0
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likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCclExeQ6LOGMD4dTsia4Ty4HtZCxRmG5vO5XIKfKX3a3vusfhHSej4Iib517vmhFW7RQgh7bpDp1yw/0, createdBy=50951609779, createdName=baihao215, createdTime=Wed May 30 07:36:03 CST 2018, time=2018-05-30, status=1, ipAttribution=)]
2018-07-08 zhaozhouchifen

#Cell#

34 0
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topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu May 31 15:05:00 CST 2018, time=2018-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320001, encodeId=c286320001a8, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIicuZyBDibwPlDRLK0NN5eJsnwhiaNemXblFCTNjAlEpSjBW9W1dFnIR5mrMMX8JHCv5ibtj5dW2v0oA/132, createdBy=d7dc2368954, createdName=林柏帆, createdTime=Wed May 30 15:37:43 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319925, encodeId=74b63199255a, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCclExeQ6LOGMD4dTsia4Ty4HtZCxRmG5vO5XIKfKX3a3vusfhHSej4Iib517vmhFW7RQgh7bpDp1yw/0, createdBy=50951609779, createdName=baihao215, createdTime=Wed May 30 07:36:03 CST 2018, time=2018-05-30, status=1, ipAttribution=)]
2018-06-23 hb2008ye

#CEL#

30 0
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topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu May 31 15:05:00 CST 2018, time=2018-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320001, encodeId=c286320001a8, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIicuZyBDibwPlDRLK0NN5eJsnwhiaNemXblFCTNjAlEpSjBW9W1dFnIR5mrMMX8JHCv5ibtj5dW2v0oA/132, createdBy=d7dc2368954, createdName=林柏帆, createdTime=Wed May 30 15:37:43 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319925, encodeId=74b63199255a, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, 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likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCclExeQ6LOGMD4dTsia4Ty4HtZCxRmG5vO5XIKfKX3a3vusfhHSej4Iib517vmhFW7RQgh7bpDp1yw/0, createdBy=50951609779, createdName=baihao215, createdTime=Wed May 30 07:36:03 CST 2018, time=2018-05-30, status=1, ipAttribution=)]
2018-06-02 1e1c07bdm01(暂无匿称)

好

56 0
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encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Sat Jun 23 01:05:00 CST 2018, time=2018-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320715, encodeId=85b6320e1590, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Sat Jun 02 06:33:46 CST 2018, time=2018-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482146, encodeId=3462148214626, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu May 31 15:05:00 CST 2018, time=2018-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320001, encodeId=c286320001a8, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIicuZyBDibwPlDRLK0NN5eJsnwhiaNemXblFCTNjAlEpSjBW9W1dFnIR5mrMMX8JHCv5ibtj5dW2v0oA/132, createdBy=d7dc2368954, createdName=林柏帆, createdTime=Wed May 30 15:37:43 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319925, encodeId=74b63199255a, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed May 30 09:21:32 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319920, encodeId=e53231992085, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Wed May 30 08:56:39 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319900, encodeId=6617319900d2, content=进展就是快啊.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCclExeQ6LOGMD4dTsia4Ty4HtZCxRmG5vO5XIKfKX3a3vusfhHSej4Iib517vmhFW7RQgh7bpDp1yw/0, createdBy=50951609779, createdName=baihao215, createdTime=Wed May 30 07:36:03 CST 2018, time=2018-05-30, status=1, ipAttribution=)]
2018-05-31 12498bb3m92(暂无昵称)

#STEM#

0 0
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2018-05-30 林柏帆

学习了.谢谢

57 0
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2018-05-30 kafei

学习了谢谢

44 0
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2018-05-30 龙胆草

学习谢谢分享

49 0
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topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu May 31 15:05:00 CST 2018, time=2018-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=320001, encodeId=c286320001a8, content=学习了.谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIicuZyBDibwPlDRLK0NN5eJsnwhiaNemXblFCTNjAlEpSjBW9W1dFnIR5mrMMX8JHCv5ibtj5dW2v0oA/132, createdBy=d7dc2368954, createdName=林柏帆, createdTime=Wed May 30 15:37:43 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319925, encodeId=74b63199255a, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed May 30 09:21:32 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319920, encodeId=e53231992085, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Wed May 30 08:56:39 CST 2018, time=2018-05-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=319900, encodeId=6617319900d2, content=进展就是快啊.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLCclExeQ6LOGMD4dTsia4Ty4HtZCxRmG5vO5XIKfKX3a3vusfhHSej4Iib517vmhFW7RQgh7bpDp1yw/0, createdBy=50951609779, createdName=baihao215, createdTime=Wed May 30 07:36:03 CST 2018, time=2018-05-30, status=1, ipAttribution=)]
2018-05-30 baihao215

进展就是快啊.学习了

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