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Blood：原发性纵膈大B细胞淋巴瘤的体细胞IL4R突变，激活JAK-STAT信号通路

2018-02-23 MedSci MedSci原创

纵膈大B细胞淋巴瘤弥漫性大B细胞淋巴瘤JAK-STAT信号通路
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原发性纵膈大B细胞淋巴瘤（PMBCL）是一种胸腺髓质B细胞起源的弥漫性大B细胞淋巴瘤的一种特殊亚型。目前该疾病的分子机制所潜在的基因突变尚未完全研究清楚。Elena Vigano等人从15例原发性PMBCL病例（总62例，24.2%）和所有PMBCL来源的细胞系中检测出新发的体细胞IL4R突变。大多数突变（11/21；52%）是在8号外显子的热点单核苷酸突变，导致跨膜区的I242N核苷酸改变。功能

原发性纵膈大B细胞淋巴瘤（PMBCL）是一种胸腺髓质B细胞起源的弥漫性大B细胞淋巴瘤的一种特殊亚型。目前该疾病的分子机制所潜在的基因突变尚未完全研究清楚。

Elena Vigano等人从15例原发性PMBCL病例（总62例，24.2%）和所有PMBCL来源的细胞系中检测出新发的体细胞IL4R突变。大多数突变（11/21；52%）是在8号外显子的热点单核苷酸突变，导致跨膜区的I242N核苷酸改变。功能分析显示该突变为功能获得性突变，导致JAK-STAT信号通路激活、下游细胞因子和B细胞特异性抗原表达水平上调。除此之外，在小鼠异种移植模型中表达I242N突变体IL4R，可使小鼠获得生长优势。

综上所述，JAK-STAT信号通路的并发突变的模式提示这些基因突变对淋巴瘤发生发展产生附加/协同效应。本研究数据提示IL4R突变，是一种新发驱动改变，为以JAK-STAT信号通路为治疗靶点提供一种强有力的临床基本原理。

原始出处：

Elena Vigano，et al.Somatic IL4R Mutations in Primary Mediastinal Large B-cell lymphoma lead to constitutive JAK-STAT signaling activation.Blood  2018  ：blood-2017-09-808907；  doi： https：//doi.org/10.1182/blood-2017-09-808907

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    2018-12-16 marlenexl

    #细胞淋巴瘤#

    0

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    2018-05-10 jiyangfei

    #原发性#

    0

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    2018-12-03 肉我只吃一口

    #JAK#

    0

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    2018-02-25 xiaoyeshuang

    #B细胞#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1702467, encodeId=0b521e024678a, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Sun Dec 16 03:23:00 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1846644, encodeId=252218466444f, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Thu May 10 08:23:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737979, encodeId=c7181e37979d4, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Mon Dec 03 01:23:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273228, encodeId=772412e3228ed, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438318, encodeId=517b143831865, content=<a href='/topic/show?id=c8a526638f6' target=_blank style='color:#2F92EE;'>#体细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539659, encodeId=fdf915396598a, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290638, encodeId=8daa2906388b, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Sun Feb 25 00:28:46 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290428, encodeId=c02b29042820, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sat Feb 24 07:48:49 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290241, encodeId=8672290241ce, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Fri Feb 23 15:37:38 CST 2018, time=2018-02-23, status=1, ipAttribution=)]
    2018-02-25 zhouqu_8

    #体细胞#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1702467, encodeId=0b521e024678a, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Sun Dec 16 03:23:00 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1846644, encodeId=252218466444f, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Thu May 10 08:23:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737979, encodeId=c7181e37979d4, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Mon Dec 03 01:23:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273228, encodeId=772412e3228ed, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438318, encodeId=517b143831865, content=<a href='/topic/show?id=c8a526638f6' target=_blank style='color:#2F92EE;'>#体细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539659, encodeId=fdf915396598a, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290638, encodeId=8daa2906388b, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Sun Feb 25 00:28:46 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290428, encodeId=c02b29042820, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sat Feb 24 07:48:49 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290241, encodeId=8672290241ce, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Fri Feb 23 15:37:38 CST 2018, time=2018-02-23, status=1, ipAttribution=)]
    2018-02-25 智者为医08

    #信号通路#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1702467, encodeId=0b521e024678a, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Sun Dec 16 03:23:00 CST 2018, time=2018-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1846644, encodeId=252218466444f, content=<a href='/topic/show?id=d3a33e0306d' target=_blank style='color:#2F92EE;'>#原发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37030, encryptionId=d3a33e0306d, topicName=原发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Thu May 10 08:23:00 CST 2018, time=2018-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1737979, encodeId=c7181e37979d4, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Mon Dec 03 01:23:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273228, encodeId=772412e3228ed, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438318, encodeId=517b143831865, content=<a href='/topic/show?id=c8a526638f6' target=_blank style='color:#2F92EE;'>#体细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26638, encryptionId=c8a526638f6, topicName=体细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1539659, encodeId=fdf915396598a, content=<a href='/topic/show?id=c61a2e315da' target=_blank style='color:#2F92EE;'>#信号通路#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27315, encryptionId=c61a2e315da, topicName=信号通路)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sun Feb 25 06:23:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290638, encodeId=8daa2906388b, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Sun Feb 25 00:28:46 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290428, encodeId=c02b29042820, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sat Feb 24 07:48:49 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290241, encodeId=8672290241ce, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Fri Feb 23 15:37:38 CST 2018, time=2018-02-23, status=1, ipAttribution=)]
    2018-02-25 忠诚向上

    好好学习一下

    0

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    2018-02-24 清风拂面

    谢谢分享学习

    0

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    2018-02-23 清风拂面

    谢谢分享学习

    0