Blood:SLAMF7high 单核细胞增多可作为埃罗妥珠单抗治疗JAK2V617F(+)骨髓纤维化患者的治疗靶点

2019-07-04 MedSci MedSci原创

近年来,单核细胞来源的纤维细胞作为骨髓纤维化(MF)的新发病机制和血清淀粉样蛋白P对纤维细胞分化的抑制作用显著改善MF预后这两点引起了人们的关注。Takaaki Maekawa等人既往发现与巨噬细胞相比,人纤维细胞高表达信号淋巴细胞活化分子- 家族7号成员(SLAMF7);对健康对照(HCs)相比,SLAMF7high 单核细胞在MF患者的外周血(PB)中显著增多。在本研究中,研究人员通过横向方法

近年来,单核细胞来源的纤维细胞作为骨髓纤维化(MF)的新发病机制和血清淀粉样蛋白P对纤维细胞分化的抑制作用显著改善MF预后这两点引起了人们的关注。Takaaki Maekawa等人既往发现与巨噬细胞相比,人纤维细胞高表达信号淋巴细胞活化分子- 家族7号成员(SLAMF7);对健康对照(HCs)相比,SLAMF7high 单核细胞在MF患者的外周血(PB)中显著增多。

在本研究中,研究人员通过横向方法评估SLAMF7high 单核细胞在HCs、无MF的骨髓增生性肿瘤(MPN)患者和有MFD骨髓增生性肿瘤(MPN)患者的PB中的比例。

结果发现携带JAK2V617F的有MF的MPN患者的SLAMF7high 单核细胞在PB中的占比明显增高,与JAK2V617F等位基因负荷呈正相关。此外,IL-1ra的血清浓度也与SLAMF7high 单核细胞的比例和JAK2V617F等位基因负荷显著相关。

上述结果表明SLAMF7high 单核细胞和IL-1ra可能都可用作发生,F的非侵袭性标志物。此外,SLAMF7high 单核细胞的JAK2V617F等位基因负荷明显高于SLAMF7low 单核细胞的JAK2V617F等位基因负荷,有望成为抗SLAMF7抗体埃罗妥珠单抗(Elo)的潜在靶点,用于治疗多发性骨髓瘤。在体外,Elo不仅能抑制HCs来源的纤维细胞分化,还能抑制MF患者来源的纤维细胞分化。Elo还能缓解罗米司亭处理所引起的小鼠MF和脾肿大。

综上所述,JAK2V617F等位基因负荷较高的slamf7高单核细胞增多与携带JAK2V617F的MPN患者发生MF有关,Elo可作为携带JAK2V617F的伴有MF的MPN患者的治疗药物。

原始出处:

Takaaki Maekawa, et al.Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab. Blood 2019 :blood.2019000051; doi: https://doi.org/10.1182/blood.2019000051

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    2020-04-17 lilili1104
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    2019-11-04 lxg951
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1895383, encodeId=73621895383e8, content=<a href='/topic/show?id=18ae64e21d3' target=_blank style='color:#2F92EE;'>#治疗靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64721, encryptionId=18ae64e21d3, topicName=治疗靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Tue Aug 20 03:29:00 CST 2019, time=2019-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2081304, encodeId=3dd820813047e, content=<a href='/topic/show?id=010e8833a1' target=_blank style='color:#2F92EE;'>#High#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8833, encryptionId=010e8833a1, topicName=High)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=afdf491, createdName=lilili1104, createdTime=Fri Apr 17 07:29:00 CST 2020, time=2020-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738008, encodeId=29d41e380081a, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, 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 Aug 19 07:29:00 CST 2019, time=2019-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2057662, encodeId=933c205e6623a, content=<a href='/topic/show?id=c02b106e29a' target=_blank style='color:#2F92EE;'>#LAM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10672, encryptionId=c02b106e29a, topicName=LAM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04ce158, createdName=lxg951, createdTime=Mon Nov 04 06:29:00 CST 2019, time=2019-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1299128, encodeId=ce3912991288c, content=<a href='/topic/show?id=2b85362063c' target=_blank style='color:#2F92EE;'>#单核细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=36206, encryptionId=2b85362063c, topicName=单核细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=daa8281, createdName=雕雕, createdTime=Sat Jul 06 09:29:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1488888, encodeId=ffc51488888fa, content=<a href='/topic/show?id=f9941022ee8' target=_blank style='color:#2F92EE;'>#JAK2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10227, encryptionId=f9941022ee8, topicName=JAK2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=666c8479565, createdName=gao_jian4220, createdTime=Sat Jul 06 09:29:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1614890, encodeId=647a16148907c, content=<a href='/topic/show?id=bc30163907f' target=_blank style='color:#2F92EE;'>#SLAMF7#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16390, encryptionId=bc30163907f, topicName=SLAMF7)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150719553947, createdName=斯嘉莉, createdTime=Sat Jul 06 09:29:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=369028, encodeId=39a83690286e, content=666, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/01/04/2540fb84decb81d47a7f2868070e6cbd.jpg, createdBy=ed3f2205793, createdName=百草, createdTime=Thu Jul 04 20:25:32 CST 2019, time=2019-07-04, status=1, ipAttribution=)]
    2019-07-06 gao_jian4220
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    2019-07-06 斯嘉莉
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    2019-07-04 百草

    666

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