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Blood：IL-7R信号——预防T-ALL复发的重要靶点！

2019-09-18 MedSci MedSci原创

IL-7RT-ALL复发
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急性T淋巴细胞白血病(T-ALL)是一种侵袭性恶性血液病，由调控胸腺T细胞发育的信号通路失调引起。复发率高，复发患者的预后极其不良。因此，开发新的特异性靶向调控白血病启动细胞（LIC）活性的通路的新疗法对治疗难治性T-ALL至关重要。白细胞介素-7受体(IL-7R)是T-ALL中普遍表达的一条重要的T细胞发育通路，与白血病的进展密切相关。但IL-7R/IL-7信号在T-ALL病理过程中的作用以及对

急性T淋巴细胞白血病(T-ALL)是一种侵袭性恶性血液病，由调控胸腺T细胞发育的信号通路失调引起。复发率高，复发患者的预后极其不良。因此，开发新的特异性靶向调控白血病启动细胞（LIC）活性的通路的新疗法对治疗难治性T-ALL至关重要。

白细胞介素-7受体(IL-7R)是T-ALL中普遍表达的一条重要的T细胞发育通路，与白血病的进展密切相关。但IL-7R/IL-7信号在T-ALL病理过程中的作用以及对该疾病复发的贡献尚未明确。为了直接探索IL-7R靶向治疗T-ALL复发是否有效，研究人员采用一种明确的NOTCH1诱导的T-ALL模型，因为大多数T-ALL患者都存在NOTCH1突变激活的情况，而NOTCH1是IL-7R表达的转录调控因子。

采用功能丧失性方法，研究人员发现用Il7r缺陷小鼠组成性激活Notch1的造血前体细胞移植到免疫缺陷小鼠上时，不能诱发白血病，而野生型小鼠的可诱发，证明了IL-7R的功能对于Notch1诱导的T细胞白血病发生必不可少。此外，研究人员还证明了IL-7R表达是具有LIC潜能的T-ALL细胞的早期功能性生物标志物，并证实IL-7R信号受损会阻碍患者来源的T-ALL移植瘤的定植和进展。值得注意的是，研究人员还发现IL-7R依赖性的LIC活性和白血病进展可以扩展到人类的B-ALL。

综上所述，本研究具有重要的治疗意义，强调了靶向IL-7R信号或可用于治疗干预，特别是预防T-ALL（和B-ALL）复发。

原始出处：

Sara González-García， et al.IL-7R is essential for leukemia-initiating cell activity and pathogenesis of T-cell acute lymphoblastic leukemia.Blood 2019 ：blood.2019000982； doi： https：//doi.org/10.1182/blood.2019000982

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  1. [GetPortalCommentsPageByObjectIdResponse(id=2058432, encodeId=6f3320584322a, content=<a href='/topic/show?id=a80d9683b5' target=_blank style='color:#2F92EE;'>#IL-7R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9683, encryptionId=a80d9683b5, topicName=IL-7R)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=845e216, createdName=cqlidoudou, createdTime=Thu Oct 31 07:46:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329282, encodeId=69c213292827c, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2328, encryptionId=bb96232801, topicName=ALL)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441320, encodeId=60941441320c9, content=<a href='/topic/show?id=67311e013a7' target=_blank style='color:#2F92EE;'>#T-ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17013, encryptionId=67311e013a7, topicName=T-ALL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b6b94820128, createdName=紫砂壶, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=)]
    2019-10-31 cqlidoudou

    #IL-7R#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2058432, encodeId=6f3320584322a, content=<a href='/topic/show?id=a80d9683b5' target=_blank style='color:#2F92EE;'>#IL-7R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9683, encryptionId=a80d9683b5, topicName=IL-7R)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=845e216, createdName=cqlidoudou, createdTime=Thu Oct 31 07:46:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329282, encodeId=69c213292827c, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2328, encryptionId=bb96232801, topicName=ALL)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441320, encodeId=60941441320c9, content=<a href='/topic/show?id=67311e013a7' target=_blank style='color:#2F92EE;'>#T-ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17013, encryptionId=67311e013a7, topicName=T-ALL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b6b94820128, createdName=紫砂壶, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=)]
    2019-09-20 膀胱癌

    #ALL#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2058432, encodeId=6f3320584322a, content=<a href='/topic/show?id=a80d9683b5' target=_blank style='color:#2F92EE;'>#IL-7R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9683, encryptionId=a80d9683b5, topicName=IL-7R)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=845e216, createdName=cqlidoudou, createdTime=Thu Oct 31 07:46:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329282, encodeId=69c213292827c, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2328, encryptionId=bb96232801, topicName=ALL)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441320, encodeId=60941441320c9, content=<a href='/topic/show?id=67311e013a7' target=_blank style='color:#2F92EE;'>#T-ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17013, encryptionId=67311e013a7, topicName=T-ALL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b6b94820128, createdName=紫砂壶, createdTime=Fri Sep 20 11:46:00 CST 2019, time=2019-09-20, status=1, ipAttribution=)]
    2019-09-20 紫砂壶

    #T-ALL#

    0