Blood:小分子BCL6抑制剂可有效治疗非硬皮病型慢性移植物抗宿主病

2018-10-07 MedSci MedSci原创

中心点:在慢性GVHD小鼠模型中,BCL6的表达对供体骨髓B/T细胞参与生发中心反应必不可少。小分子BCL6抑制剂可调节转录抑制,代表了慢性GVHD的一种新的治疗策略。摘要:类固醇依赖性或难治性cGCHD患者预后不良,仅依鲁替尼获得FDA批准用于该并发症。cGVHD通常是由生发中心(GC)反应所驱动的,在此反应中,滤泡辅助T细胞与GC B细胞相互作用,产生与疾病发病过程相关的抗体。转录共抑制剂BC

中心点:

在慢性GVHD小鼠模型中,BCL6的表达对供体骨髓B/T细胞参与生发中心反应必不可少。

小分子BCL6抑制剂可调节转录抑制,代表了慢性GVHD的一种新的治疗策略。

摘要:

类固醇依赖性或难治性cGCHD患者预后不良,仅依鲁替尼获得FDA批准用于该并发症。cGVHD通常是由生发中心(GC)反应所驱动的,在此反应中,滤泡辅助T细胞与GC B细胞相互作用,产生与疾病发病过程相关的抗体。

转录共抑制剂BCL6是BTB/POZ转录因子家族的成员,是GC反应中免疫细胞的主要调控因子。研究人员发现BCL6在供体T细胞和B细胞中的表达对cGVHD的发展必不可少,提示BCL6或可作为cGVHD的治疗靶点。

小分子BCL6抑制剂可逆转与强烈的GC反应相关的闭塞性细支气管炎的多器官系统损伤小鼠模型的活跃的cGVHD,但对以硬皮病为主要表现的cGVHD小鼠模型没有明显疗效。

对于由抗体驱动cGVHD的cGVHD患者,靶向BCL6代表一种新的特异性针对GC调控的治疗方法,可拓展至当下可用的二线药物。


原始出处:

Katelyn Paz, et al. Small-molecule BCL6 inhibitor effectively treats mice with non-sclerodermatous chronic graft-versus-host disease. Blood  2018  :blood-2018-03-839993;  doi: https://doi.org/10.1182/blood-2018-03-839993

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    2019-07-24 宋威
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createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419722, encodeId=f1a81419e2263, content=<a href='/topic/show?id=a798e520582' target=_blank style='color:#2F92EE;'>#移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75205, encryptionId=a798e520582, topicName=移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4d6c3527534, createdName=手留余香, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578848, encodeId=662915e88489d, content=<a href='/topic/show?id=7e74536097a' target=_blank style='color:#2F92EE;'>#慢性移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53609, encryptionId=7e74536097a, topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619526, encodeId=335d161952642, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=)]
    2019-06-15 jklm09
  5. 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topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619526, encodeId=335d161952642, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=)]
    2019-01-11 xuyong535
  6. 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topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619526, encodeId=335d161952642, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=)]
    2018-10-09 rgjl
  7. 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createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1419722, encodeId=f1a81419e2263, content=<a href='/topic/show?id=a798e520582' target=_blank style='color:#2F92EE;'>#移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75205, encryptionId=a798e520582, topicName=移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4d6c3527534, createdName=手留余香, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578848, encodeId=662915e88489d, content=<a href='/topic/show?id=7e74536097a' target=_blank style='color:#2F92EE;'>#慢性移植物抗宿主病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53609, encryptionId=7e74536097a, topicName=慢性移植物抗宿主病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e2dc16449103, createdName=丁鹏鹏, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619526, encodeId=335d161952642, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Tue Oct 09 04:20:00 CST 2018, time=2018-10-09, status=1, ipAttribution=)]
    2018-10-09 wincls
  8. 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  9. 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  10. 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