肿瘤科

订阅

MedSci主页 / 所有栏目 / 肿瘤科

Blood：RUNX1和CBFβ-SMMHC共同反式激活异常髓系祖细胞促进白血病的发生

2020-10-12 星云 MedSci原创

白血病RUNX1CBFβ-SMMHC
关注

16号染色体倒置是M4亚型急性髓系白血病伴嗜酸粒细胞增多症(AML M4Eo)患者一致的特征，它产生了CBFB-MYH11融合基因。

16号染色体倒置是M4亚型急性髓系白血病伴嗜酸粒细胞增多症(AML M4Eo)患者一致的特征，它产生了CBFB-MYH11融合基因。一般认为由CBFB-MYH11融合基因编码的融合蛋白CBFβ-SMMHC是RUNX1的显性负抑制因子。

然而，近期的研究结果挑战了CBFβ-SMMHC介导的白血病发生的RUNX1抑制模型。

为了明确Runx1在CBFB-MYH11诱导的白血病中的作用，研究人员将条件敲除Runx1基因的小鼠(Runx1f/f)与条件性Cbfb-MYH11敲入小鼠(Cbfb+/56M)进行杂交。

pIpC处理后不同小鼠的存活期

经Poly(I:C，pIpC)注射诱导造血细胞的Mx1-Cre活化后，Mx1-CreCbfb+/56M小鼠在5个月内全部发生了白血病，而Runx1f/fMx1-CreCbfb+/56M小鼠均未发生白血病，且这种作用是细胞自主性的。

pIpC治疗不同时间后AMP细胞占骨髓细胞的比例

重要的是，在Runx1f/fMx1-CreCbfb+/56M小鼠中，Cbfb-MYH11诱导的白血病起始细胞群——异常髓系祖细胞(AMPs)减少甚至消失。AMP细胞的RNA-seq分析表明，Mx1-CreCbfb+/56M和Runx1f/fMx1-CreCbfb+/56M小鼠的增殖、分化阻滞和白血病起始相关基因均差异性表达。

此外，通过染色质免疫切割测序(ChIC-seq)，研究人员观察到RUNX1/CBFβ-SMMHC靶基因在Runx1f/fMx1-CreCbfb+/56m细胞中显著富集，尤其是在下调的基因中，提示RUNX1和CBFβ-SMMHC主要通过直接结合靶基因而共同发挥基因表达的激活作用。

综上所述，本研究表明，Runx1在Cbfb-MYH11诱导的白血病发生过程中不可或缺，它与CBFβ-SMMHC共同调节与生成功能性AMP群体相关的关键基因。

原始出处：

Zhen Tao,Cao Yaqiang,Ren Gang et al. RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development.[J] .Blood, 2020, undefined: undefined.

版权声明：
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料，版权均属于梅斯医学所有。非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章，或“梅斯号”自媒体发布的文章，仅系出于传递更多信息之目的，本站仅负责审核内容合规，其内容不代表本站立场，本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1993657, encodeId=53c0199365e46, content=<a href='/topic/show?id=044d1166997' target=_blank style='color:#2F92EE;'>#MHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11669, encryptionId=044d1166997, topicName=MHC)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/uiafWKNzZJdibyrrAR5YyVBUCbj0fhAekic1Tou5YEI9IBoJ1QrGpZylYAkiafDNofZkNHJCPTpY1HK14LvuFzD5xQ/132, createdBy=706e2500208, createdName=ms9203727104890838, createdTime=Sun Sep 12 09:50:41 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512483, encodeId=59a01512483dc, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569816, encodeId=789a15698162c, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15740, encryptionId=5d8315e409c, topicName=RUNX1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=093515566995, createdName=soongzhihua, createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891649, encodeId=7513891649b4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc854765440, createdName=1256062000, createdTime=Mon Oct 12 23:56:18 CST 2020, time=2020-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891641, encodeId=e0f1891641ae, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08b05417659, createdName=ms1000000408798788, createdTime=Mon Oct 12 22:56:34 CST 2020, time=2020-10-12, status=1, ipAttribution=)]
    2021-09-12 ms9203727104890838

    #MHC#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1993657, encodeId=53c0199365e46, content=<a href='/topic/show?id=044d1166997' target=_blank style='color:#2F92EE;'>#MHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11669, encryptionId=044d1166997, topicName=MHC)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/uiafWKNzZJdibyrrAR5YyVBUCbj0fhAekic1Tou5YEI9IBoJ1QrGpZylYAkiafDNofZkNHJCPTpY1HK14LvuFzD5xQ/132, createdBy=706e2500208, createdName=ms9203727104890838, createdTime=Sun Sep 12 09:50:41 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512483, encodeId=59a01512483dc, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569816, encodeId=789a15698162c, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15740, encryptionId=5d8315e409c, topicName=RUNX1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=093515566995, createdName=soongzhihua, createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891649, encodeId=7513891649b4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc854765440, createdName=1256062000, createdTime=Mon Oct 12 23:56:18 CST 2020, time=2020-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891641, encodeId=e0f1891641ae, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08b05417659, createdName=ms1000000408798788, createdTime=Mon Oct 12 22:56:34 CST 2020, time=2020-10-12, status=1, ipAttribution=)]
    2020-10-14 12498636m52(暂无昵称)

    #祖细胞#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1993657, encodeId=53c0199365e46, content=<a href='/topic/show?id=044d1166997' target=_blank style='color:#2F92EE;'>#MHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11669, encryptionId=044d1166997, topicName=MHC)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/uiafWKNzZJdibyrrAR5YyVBUCbj0fhAekic1Tou5YEI9IBoJ1QrGpZylYAkiafDNofZkNHJCPTpY1HK14LvuFzD5xQ/132, createdBy=706e2500208, createdName=ms9203727104890838, createdTime=Sun Sep 12 09:50:41 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512483, encodeId=59a01512483dc, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569816, encodeId=789a15698162c, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15740, encryptionId=5d8315e409c, topicName=RUNX1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=093515566995, createdName=soongzhihua, createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891649, encodeId=7513891649b4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc854765440, createdName=1256062000, createdTime=Mon Oct 12 23:56:18 CST 2020, time=2020-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891641, encodeId=e0f1891641ae, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08b05417659, createdName=ms1000000408798788, createdTime=Mon Oct 12 22:56:34 CST 2020, time=2020-10-12, status=1, ipAttribution=)]
    2020-10-14 soongzhihua

    #RUNX1#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1993657, encodeId=53c0199365e46, content=<a href='/topic/show?id=044d1166997' target=_blank style='color:#2F92EE;'>#MHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11669, encryptionId=044d1166997, topicName=MHC)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/uiafWKNzZJdibyrrAR5YyVBUCbj0fhAekic1Tou5YEI9IBoJ1QrGpZylYAkiafDNofZkNHJCPTpY1HK14LvuFzD5xQ/132, createdBy=706e2500208, createdName=ms9203727104890838, createdTime=Sun Sep 12 09:50:41 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512483, encodeId=59a01512483dc, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569816, encodeId=789a15698162c, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15740, encryptionId=5d8315e409c, topicName=RUNX1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=093515566995, createdName=soongzhihua, createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891649, encodeId=7513891649b4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc854765440, createdName=1256062000, createdTime=Mon Oct 12 23:56:18 CST 2020, time=2020-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891641, encodeId=e0f1891641ae, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08b05417659, createdName=ms1000000408798788, createdTime=Mon Oct 12 22:56:34 CST 2020, time=2020-10-12, status=1, ipAttribution=)]
    2020-10-12 1256062000

    学习

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1993657, encodeId=53c0199365e46, content=<a href='/topic/show?id=044d1166997' target=_blank style='color:#2F92EE;'>#MHC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11669, encryptionId=044d1166997, topicName=MHC)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/uiafWKNzZJdibyrrAR5YyVBUCbj0fhAekic1Tou5YEI9IBoJ1QrGpZylYAkiafDNofZkNHJCPTpY1HK14LvuFzD5xQ/132, createdBy=706e2500208, createdName=ms9203727104890838, createdTime=Sun Sep 12 09:50:41 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512483, encodeId=59a01512483dc, content=<a href='/topic/show?id=f802e4102cb' target=_blank style='color:#2F92EE;'>#祖细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74102, encryptionId=f802e4102cb, topicName=祖细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f18310470858, createdName=12498636m52(暂无昵称), createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569816, encodeId=789a15698162c, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15740, encryptionId=5d8315e409c, topicName=RUNX1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=093515566995, createdName=soongzhihua, createdTime=Wed Oct 14 13:50:41 CST 2020, time=2020-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891649, encodeId=7513891649b4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=dc854765440, createdName=1256062000, createdTime=Mon Oct 12 23:56:18 CST 2020, time=2020-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=891641, encodeId=e0f1891641ae, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08b05417659, createdName=ms1000000408798788, createdTime=Mon Oct 12 22:56:34 CST 2020, time=2020-10-12, status=1, ipAttribution=)]
    2020-10-12 ms1000000408798788

    好

    0

相关资讯

Brit J Cancer：成人白血病与长期空气污染暴露之间的关系

在老年人中，较高的白血病风险与诊断前1年、5年和10年较高的平均PM2.5浓度有关。

同种异体CAR-T细胞疗法治疗白血病，获得FDA的快速通道指定

同种异体嵌合抗原受体（CAR-T）细胞疗法PBCAR0191治疗晚期前体B细胞急性淋巴细胞白血病，获得FDA快速通道指定。

世界首例艾滋病治愈者——“柏林病人”白血病复发

日前，世界首例艾滋病治愈者——曾被称为“柏林病人”的蒂莫西·雷·布朗(Timothy Ray Brown)因白血病复发进入晚

肚子越来越大，爱韩剧的少女竟得了“女主病”？！专家说，白血病不都是绝症！

18岁少女彤彤（化名）是个资深的“哈韩族”，

Br J Cancer：长期暴露于PM2.5污染中会增加老年人白血病发病风险

白血病是一种骨髓癌，在2012年至2016年期间，丹麦每年每10万人的年龄标准发生率为男性10.7、女性7.2。在过去的10年中，该比率处于稳定状态。白血病可分为急性或慢性的，主要有淋巴性和骨髓性两种

亚盛医药Bcl-2抑制剂再获FDA孤儿药资格认定，治疗慢性淋巴细胞白血病

9月7日，亚盛医药宣布，FDA授予其在研原创新药Bcl-2抑制剂APG-2575孤儿药资格认定，用于治疗慢性淋巴细胞白血病（CLL）。这是APG-2575获得的第二个FDA授予的孤儿药资格认定。今年7