Leukemia:免疫介导的获得性再生障碍性贫血患者的T细胞基因突变分析

2021-04-06 xiaozeng MedSci原创

获得性再生障碍性贫血(AA)是一种免疫介导的骨髓衰竭综合征,其是由细胞毒性T细胞破坏造血干/祖细胞(HSPC)所引起的。

获得性再生障碍性贫血(AA)是一种免疫介导的骨髓衰竭综合征,其是由细胞毒性T细胞破坏造血干/祖细胞(HSPC)所引起的。

免疫介导的AA的主要特征为HSPCs的克隆改变:X染色体失活偏移、细胞遗传异常、6p染色体的单亲二倍性、体细胞中PIG-A基因突变引起的阵发性睡眠性血红蛋白尿症以及克隆性造血(CH)相关基因的体细胞突变。


既往研究显示,在AA患者中经常能够检测到寡克隆的CD8+T细胞,其能够诱导同源HSPC细胞的凋亡。此外,AA患者中异常活跃的T细胞与疾病的发生发展息息相关,然而其在HSPC细胞中的抗原性靶标目前仍然未知。

在该研究中,研究人员通过对24名AA患者的CD4+和CD8+T细胞进行测序,并将测序结果与??20名健康对照和37名AA患者的全外显子组测序结果进行比对,旨在分析AA患者T细胞中2533个基因的突变情况。


研究人员发现,体细胞突变在患者和健康对照者中均很常见,但在AA患者的CD8+T细胞中富集,该细胞在JAK-STAT和MAPK通路中富集了最多的基因突变。通过T细胞受体β测序评估发现,基因突变负担也与CD8+T细胞的克隆性相关。

AA患者CD4+或CD8+T细胞中JAK-STAT通路基因突变

为了进一步了解突变的影响,研究人员对携带STAT3突变或CD8+T细胞中其他基因突变的AA患者进行了单细胞测序。结果显示,STAT3突变的克隆具有细胞毒性,其可以与其他CD8+T细胞明显区分开,而该细胞毒性可被成功的免疫抑制治疗所削弱。


总而言之,该研究结果揭示,T细胞中的体细胞突变较为常见的,且与细胞的克隆性相关,并能够改变T细胞表型,因此有必要进一步研究其在AA发病机制中的作用。


原始出处:

Lundgren, S., Keränen, M.A.I., Kankainen, M. et al. Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia. Leukemia (30 March 2021).

 

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  1. [GetPortalCommentsPageByObjectIdResponse(id=2042682, encodeId=3e562042682f2, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Wed Aug 18 02:40:24 CST 2021, time=2021-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=955337, encodeId=4ccc95533e06, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3c31528806, createdName=gqylhd, createdTime=Thu Apr 08 23:12:40 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954409, encodeId=a170954409e1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=75a45462359, createdName=ms1000001691009964, createdTime=Wed Apr 07 09:35:49 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954374, encodeId=a5479543e4b1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e3f5293425, createdName=1486adbfm03暂无昵称, createdTime=Wed Apr 07 08:10:04 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954361, encodeId=e4e19543613d, content=好文章,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Wed Apr 07 06:32:45 CST 2021, time=2021-04-07, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=2042682, encodeId=3e562042682f2, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Wed Aug 18 02:40:24 CST 2021, time=2021-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=955337, encodeId=4ccc95533e06, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3c31528806, createdName=gqylhd, createdTime=Thu Apr 08 23:12:40 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954409, encodeId=a170954409e1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=75a45462359, createdName=ms1000001691009964, createdTime=Wed Apr 07 09:35:49 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954374, encodeId=a5479543e4b1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e3f5293425, createdName=1486adbfm03暂无昵称, createdTime=Wed Apr 07 08:10:04 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954361, encodeId=e4e19543613d, content=好文章,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Wed Apr 07 06:32:45 CST 2021, time=2021-04-07, status=1, ipAttribution=)]
    2021-04-08 gqylhd

    学习了

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2042682, encodeId=3e562042682f2, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Wed Aug 18 02:40:24 CST 2021, time=2021-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=955337, encodeId=4ccc95533e06, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3c31528806, createdName=gqylhd, createdTime=Thu Apr 08 23:12:40 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954409, encodeId=a170954409e1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=75a45462359, createdName=ms1000001691009964, createdTime=Wed Apr 07 09:35:49 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954374, encodeId=a5479543e4b1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e3f5293425, createdName=1486adbfm03暂无昵称, createdTime=Wed Apr 07 08:10:04 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954361, encodeId=e4e19543613d, content=好文章,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Wed Apr 07 06:32:45 CST 2021, time=2021-04-07, status=1, ipAttribution=)]
    2021-04-07 ms1000001691009964

    学习

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2042682, encodeId=3e562042682f2, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Wed Aug 18 02:40:24 CST 2021, time=2021-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=955337, encodeId=4ccc95533e06, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3c31528806, createdName=gqylhd, createdTime=Thu Apr 08 23:12:40 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954409, encodeId=a170954409e1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=75a45462359, createdName=ms1000001691009964, createdTime=Wed Apr 07 09:35:49 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954374, encodeId=a5479543e4b1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e3f5293425, createdName=1486adbfm03暂无昵称, createdTime=Wed Apr 07 08:10:04 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954361, encodeId=e4e19543613d, content=好文章,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Wed Apr 07 06:32:45 CST 2021, time=2021-04-07, status=1, ipAttribution=)]
    2021-04-07 1486adbfm03暂无昵称

    好文章

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2042682, encodeId=3e562042682f2, content=<a href='/topic/show?id=999c88014ea' target=_blank style='color:#2F92EE;'>#获得性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88014, encryptionId=999c88014ea, topicName=获得性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Wed Aug 18 02:40:24 CST 2021, time=2021-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=955337, encodeId=4ccc95533e06, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3c31528806, createdName=gqylhd, createdTime=Thu Apr 08 23:12:40 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954409, encodeId=a170954409e1, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=75a45462359, createdName=ms1000001691009964, createdTime=Wed Apr 07 09:35:49 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954374, encodeId=a5479543e4b1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9e3f5293425, createdName=1486adbfm03暂无昵称, createdTime=Wed Apr 07 08:10:04 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=954361, encodeId=e4e19543613d, content=好文章,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Wed Apr 07 06:32:45 CST 2021, time=2021-04-07, status=1, ipAttribution=)]
    2021-04-07 yangchou

    好文章,谢谢分享

    0

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