Leukemia:重磅!有望通过调控JAK/STAT信号通路减少T-ALL患者糖皮质激素抵抗!

2017-12-29 MedSci MedSci原创

IL-7受体/JAK/STAT的其他抑制剂可以提高一类T-ALL治疗中的糖皮质激素的效果。

T细胞淋巴细胞白血病来源于胸腺T前体细胞的恶性转化。强化治疗使儿童患者的生存期治疗效果有了长足的提高,但是复发性或难治性T-ALL患者的5年生存率小于10%。并且有利于治疗的可标记高危型的生物标志在疾病的早期治疗中应用受限。更重要的是,新确诊的病人在首次接受化疗后常有微小残留病灶,或者在泼尼松治疗前期不能快速清除外周的白血病原始细胞从而造成疾病预后差。

前期的研究表明糖皮质激素抵抗在复发患者治疗过程中较常见,并且糖皮质激素抵抗现象较其他化疗药物的抵抗更常见,这也提示增强高危患者对糖皮质激素的敏感性对此类疾病的治疗有重要意义。

糖皮质激素(glucocorticoids, GCs)与糖皮质激素受体形成复合物转运到细胞核,它们在细胞核中参与调控细胞周期和凋亡相关的基因表达。但是T-ALL病人中糖皮质激素抵抗的机制研究并不明确,而这成为克服糖皮质激素抵抗的主要障碍。

T-ALL细胞具有基因异质性,这导致基因异常不能成为疾病危险分级的依据。但是研究者推测这些基因病变也许会集中体现在T-ALL疾病亚型的某些生化改变中,而这些疾病亚型细胞会具有相同的化疗药物抵抗机制。研究者在体外细胞水平的实验中发现早期胸腺前体细胞(early thymic precursor,ETP)阶段来源的T-ALL以及一些非胸腺前体细胞(non-ETP)T-ALL常出现原发性的糖皮质激素抵抗。GC抵抗的非ETP T-ALL细胞在IL-7的刺激下JAK/STAT信号通路出现强烈应答。去除培养环境中的IL-7或者添加JAK/STAT信号通路的抑制剂可以提高T-ALL细胞对糖皮质激素的敏感性。结合使用糖皮质激素地塞米松和JAK1/2抑制剂鲁索替尼能够改善IL-7依赖的糖皮质激素抵抗细胞中前凋亡因子和抗凋亡因子之间的平衡,但是对非IL-7依赖的糖皮质激素抵抗没有作用。

总之,这些研究表明应用鲁索替尼或者IL-7受体/JAK/STAT信号通路的其他抑制剂可以提高某一类T-ALL治疗中糖皮质激素的效果。


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    2018-01-16 1e145228m78(暂无匿称)

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    0

  4. 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createdName=xxxx1054, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600306, encodeId=792f160030669, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2018-01-07 大爰

    学习并分享!!

    0

  5. 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createdName=xxxx1054, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600306, encodeId=792f160030669, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2018-01-04 三生有幸9135

    学习一下谢谢分享

    0

  6. 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createdName=xxxx1054, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600306, encodeId=792f160030669, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2017-12-30 膀胱癌
  7. 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createdName=xxxx1054, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600306, encodeId=792f160030669, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2017-12-30 紫砂壶
  8. 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  9. 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createdName=xxxx1054, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600306, encodeId=792f160030669, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Dec 30 23:25:00 CST 2017, time=2017-12-30, status=1, ipAttribution=)]
    2017-12-30 xxxx1054
  10. 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新加坡国立大学(NUS)癌症科学研究所首席调查员,新加坡国立医学大学医学院医学系主任研究员助理教授桑卡斯·桑达(Naka Yong Loo Lin)医学研究小组提供了新的见解,关于如何在正常的 T 细胞发育过程中产生基因,并促成白血病的形成。研究结果已发表在白血病杂志上。T 细胞是一种在胸腺中发育的白细胞(因此命名为 T 细胞),一种原发性淋巴器官。这些细胞在身体的细胞防御系统中起着不可或缺的作用