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Blood：GNAO1突变和ETV6-RUNX1融合变异促进白血病发生的协同作用

2020-09-19 QQY MedSci原创

全外显子测序白血病发生GNAO1突变ETV6-RUNX1融合
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对ALL双胞胎患者进行全外显子测序发现GNAO1 R209C突变是ETV6-RUNX1阳性白血病前期的新二次打击；E/R融合和GNAO1 R209C突变表达的相互激活通过激活PI3K通路促进白血病发生

白血病发生的特点是染色体重排与额外的分子断裂，但这两者之间的合作机制仍不清楚。

近期发表在《Blood》杂志上的“dentification of functional cooperative mutations of GNAO1 in human acute lymphoblastic leukemia”一文中，研究人员对一对ETV6-RUNX1 (E/R)基因融合不一致的儿童急性淋巴细胞白血病(ALL)单卵双胞胎进行了全外显子测序。

测序结果发现，G蛋白α亚基o1的R209C突变是ALL的一个新的风险位点。此外，GNAO1错义突变仅发生于ALL患者，与E/R融合相关。异位表达GNAO1 R209C突变体可增加其GTPase活性，促进细胞增殖和细胞肿瘤转化。

结合E/R融合，GNAO1 R209C突变通过激活PI3K/Akt/mTOR信号促进白血病发生。反过来，活化的mTORC1磷酸化p300乙酰转移酶，进而使E/R乙酰化，从而增强GNAO1 R209C的E/R转录活性。

总而言之，该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。

原始出处：

Lili Song, et a. Identification of functional cooperative mutations of GNAO1 in human acute lymphoblastic leukemia. Blood. September 08, 2020.

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    2021-05-20 huperzia

    #白血病发生#

    0

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    2020-10-01 d830372

    #Etv6#

    0

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    2020-09-21 12498dabm77暂无昵称

    #变异#

    0

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    2020-09-21 licz0427

    #融合#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1717440, encodeId=ba611e17440cc, content=<a href='/topic/show?id=6089e177842' target=_blank style='color:#2F92EE;'>#白血病发生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71778, encryptionId=6089e177842, topicName=白血病发生)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=961832410013, createdName=huperzia, createdTime=Thu May 20 12:16:26 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785865, encodeId=30371e8586503, content=<a href='/topic/show?id=421be07215' target=_blank style='color:#2F92EE;'>#Etv6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7072, encryptionId=421be07215, topicName=Etv6)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 01 10:16:26 CST 2020, time=2020-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342732, encodeId=63471342e32f9, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525554, encodeId=b085152555420, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569815, encodeId=260e156981515, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886725, encodeId=3422886e25dd, content=该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Sat Sep 19 22:29:07 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886704, encodeId=224e886e040c, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4e3c5419578, createdName=ms4000001323716235, createdTime=Sat Sep 19 19:44:58 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886693, encodeId=add3886693ec, content=吃吃吃v分, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e855419670, createdName=ms4000001311767518, createdTime=Sat Sep 19 17:37:54 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886662, encodeId=82f788666233, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3c94673625, createdName=1121790150, createdTime=Sat Sep 19 15:14:26 CST 2020, time=2020-09-19, status=1, ipAttribution=)]
    2020-09-21 soongzhihua

    #RUNX1#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1717440, encodeId=ba611e17440cc, content=<a href='/topic/show?id=6089e177842' target=_blank style='color:#2F92EE;'>#白血病发生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71778, encryptionId=6089e177842, topicName=白血病发生)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=961832410013, createdName=huperzia, createdTime=Thu May 20 12:16:26 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785865, encodeId=30371e8586503, content=<a href='/topic/show?id=421be07215' target=_blank style='color:#2F92EE;'>#Etv6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7072, encryptionId=421be07215, topicName=Etv6)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 01 10:16:26 CST 2020, time=2020-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342732, encodeId=63471342e32f9, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525554, encodeId=b085152555420, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569815, encodeId=260e156981515, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886725, encodeId=3422886e25dd, content=该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Sat Sep 19 22:29:07 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886704, encodeId=224e886e040c, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4e3c5419578, createdName=ms4000001323716235, createdTime=Sat Sep 19 19:44:58 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886693, encodeId=add3886693ec, content=吃吃吃v分, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e855419670, createdName=ms4000001311767518, createdTime=Sat Sep 19 17:37:54 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886662, encodeId=82f788666233, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3c94673625, createdName=1121790150, createdTime=Sat Sep 19 15:14:26 CST 2020, time=2020-09-19, status=1, ipAttribution=)]
    2020-09-19 Nebula-Qin

    该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1717440, encodeId=ba611e17440cc, content=<a href='/topic/show?id=6089e177842' target=_blank style='color:#2F92EE;'>#白血病发生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71778, encryptionId=6089e177842, topicName=白血病发生)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=961832410013, createdName=huperzia, createdTime=Thu May 20 12:16:26 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785865, encodeId=30371e8586503, content=<a href='/topic/show?id=421be07215' target=_blank style='color:#2F92EE;'>#Etv6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7072, encryptionId=421be07215, topicName=Etv6)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 01 10:16:26 CST 2020, time=2020-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342732, encodeId=63471342e32f9, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525554, encodeId=b085152555420, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569815, encodeId=260e156981515, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886725, encodeId=3422886e25dd, content=该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Sat Sep 19 22:29:07 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886704, encodeId=224e886e040c, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4e3c5419578, createdName=ms4000001323716235, createdTime=Sat Sep 19 19:44:58 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886693, encodeId=add3886693ec, content=吃吃吃v分, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e855419670, createdName=ms4000001311767518, createdTime=Sat Sep 19 17:37:54 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886662, encodeId=82f788666233, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3c94673625, createdName=1121790150, createdTime=Sat Sep 19 15:14:26 CST 2020, time=2020-09-19, status=1, ipAttribution=)]
    2020-09-19 ms4000001323716235

    厉害了👍

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1717440, encodeId=ba611e17440cc, content=<a href='/topic/show?id=6089e177842' target=_blank style='color:#2F92EE;'>#白血病发生#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71778, encryptionId=6089e177842, topicName=白血病发生)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=961832410013, createdName=huperzia, createdTime=Thu May 20 12:16:26 CST 2021, time=2021-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785865, encodeId=30371e8586503, content=<a href='/topic/show?id=421be07215' target=_blank style='color:#2F92EE;'>#Etv6#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7072, encryptionId=421be07215, topicName=Etv6)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80a244, createdName=d830372, createdTime=Thu Oct 01 10:16:26 CST 2020, time=2020-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342732, encodeId=63471342e32f9, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1525554, encodeId=b085152555420, content=<a href='/topic/show?id=08548885835' target=_blank style='color:#2F92EE;'>#融合#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88858, encryptionId=08548885835, topicName=融合)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=08a911636812, createdName=licz0427, createdTime=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569815, encodeId=260e156981515, content=<a href='/topic/show?id=5d8315e409c' target=_blank style='color:#2F92EE;'>#RUNX1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Mon Sep 21 05:16:26 CST 2020, time=2020-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886725, encodeId=3422886e25dd, content=该研究为GNAO1突变和E/R融合的功能性合作提供了临床证据，提示GNAO1可能是人白血病的潜在治疗靶点。, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210725/69b5882b3c3845c19efa131b4ff8b1f7/06ccd8f1857e4e14862049ab235618eb.jpg, createdBy=74c72110107, createdName=Nebula-Qin, createdTime=Sat Sep 19 22:29:07 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886704, encodeId=224e886e040c, content=厉害了👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=106, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4e3c5419578, createdName=ms4000001323716235, createdTime=Sat Sep 19 19:44:58 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886693, encodeId=add3886693ec, content=吃吃吃v分, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0e855419670, createdName=ms4000001311767518, createdTime=Sat Sep 19 17:37:54 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=886662, encodeId=82f788666233, content=嗯, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3c94673625, createdName=1121790150, createdTime=Sat Sep 19 15:14:26 CST 2020, time=2020-09-19, status=1, ipAttribution=)]
    2020-09-19 ms4000001311767518

    吃吃吃v分

    0

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    2020-09-19 1121790150

    嗯

    0

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