Baidu
map

Blood:靶向PRMT1介导的FLT3甲基化可增强MLL重排的ALL细胞的清除

2021-06-10 Nebula MedSci原创

通过抑制PRMT1来消除FLT3精氨酸甲基化代表了一种有希望的靶向MLL-r ALL细胞的治疗策略

中心点:

PRMT1高表达通过调节R972/973处的FLT3甲基化维持MLL-r ALL细胞存活和生长。

PRMT1抑制可增强酪氨酸激酶抑制剂治疗对MLL-r ALL的清除。

复发仍是 MLL 重排 (MLL-r) 的急性淋巴细胞白血病 (ALL) 治疗失败的主要原因,复发原因主要是常规化疗或靶向治疗后耐药性克隆的持续存在。因此,明确MLL-r ALL潜在的维持机制对于开发新的有效治疗至关重要。

PRMT1,可在组蛋白/非组蛋白上沉积形成不对称二甲基精氨酸标记,据报道在各种癌症中过度表达

PRMT1在MLL-r ALL细胞中高表达

在该研究中,研究人员发现PRMT1在MLL-r ALL细胞中的表达水平升高,并证明了PRMT1抑制可显著抑制白血病细胞的生长和存活

抑制PRMT1可抑制白血病细胞的生长和存活

在机制上,PRMT1使精氨酸 (R) 残基 972 和 973 (R972/973) 处的Fms 样受体酪氨酸激酶3 (FLT3)甲基化,通过FLT3 甲基化依赖性的方式在 MLL-r ALL 细胞中发挥致癌作用。生物化学和计算分析都表明R972/973甲基化可以促进接头蛋白以磷酸酪氨酸 (Y) 残基 969 (Y969) 依赖性或独立的方式募集到FLT3上。

移植不同FLT3缺陷细胞的移植瘤小鼠的存活率

与Y969磷酸化缺陷的FLT3转导细胞相比,表达R972/973甲基化缺陷的FLT3的细胞表现出更强的细胞凋亡和生长抑制。此外,研究人员还发现,I型PRMT抑制剂MS023抑制白血病细胞活力的能力与基线FLT3 R972/973 甲基化水平平行。

不同方案治疗的移植瘤小鼠的存活率

最后,在患者来源的小鼠异种移植瘤中,与单用FLT3酪氨酸激酶抑制剂PKC412治疗相比,PKC412与MS023联合治疗可增强MLL-r ALL细胞的清除

总结示意图

综上,该研究结果表明,通过抑制PRMT1来消除FLT3精氨酸甲基化代表了一种有希望的靶向MLL-r ALL细胞的治疗策略

原始出处:

Yinghui Zhu, et al. Targeting PRMT1-mediated FLT3 methylation disrupts maintenance of MLL-rearranged acute lymphoblastic leukemia. Blood (2019) 134 (15): 1257–1268. https://doi.org/10.1182/blood.2019002457

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1329513, encodeId=72531329513f6, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, 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=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538900, encodeId=08a915389008c, content=<a href='/topic/show?id=5f04e51467' target=_blank style='color:#2F92EE;'>#FLT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7514, encryptionId=5f04e51467, topicName=FLT3)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=57a713069145, createdName=fengyi816, createdTime=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972851, encodeId=f3dc9e2851a7, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210610/41ac025ada93475188bc6172c56dae78/0ec9ad5bce4c43dabd50e6457b8b9e3c.jpg, createdBy=41945518358, createdName=包包123, createdTime=Fri Jun 11 14:50:43 CST 2021, time=2021-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972675, encodeId=fc949e26756d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=67634708538, createdName=1356548325, createdTime=Thu Jun 10 22:08:55 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-12 膀胱癌
  2. [GetPortalCommentsPageByObjectIdResponse(id=1329513, encodeId=72531329513f6, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, 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=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538900, encodeId=08a915389008c, content=<a href='/topic/show?id=5f04e51467' target=_blank style='color:#2F92EE;'>#FLT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7514, encryptionId=5f04e51467, topicName=FLT3)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=57a713069145, createdName=fengyi816, createdTime=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972851, encodeId=f3dc9e2851a7, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210610/41ac025ada93475188bc6172c56dae78/0ec9ad5bce4c43dabd50e6457b8b9e3c.jpg, createdBy=41945518358, createdName=包包123, createdTime=Fri Jun 11 14:50:43 CST 2021, time=2021-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972675, encodeId=fc949e26756d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=67634708538, createdName=1356548325, createdTime=Thu Jun 10 22:08:55 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-12 fengyi816
  3. [GetPortalCommentsPageByObjectIdResponse(id=1329513, encodeId=72531329513f6, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, 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=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538900, encodeId=08a915389008c, content=<a href='/topic/show?id=5f04e51467' target=_blank style='color:#2F92EE;'>#FLT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7514, encryptionId=5f04e51467, topicName=FLT3)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=57a713069145, createdName=fengyi816, createdTime=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972851, encodeId=f3dc9e2851a7, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210610/41ac025ada93475188bc6172c56dae78/0ec9ad5bce4c43dabd50e6457b8b9e3c.jpg, createdBy=41945518358, createdName=包包123, createdTime=Fri Jun 11 14:50:43 CST 2021, time=2021-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972675, encodeId=fc949e26756d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=67634708538, createdName=1356548325, createdTime=Thu Jun 10 22:08:55 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-11 包包123

    看看

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1329513, encodeId=72531329513f6, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, 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=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1538900, encodeId=08a915389008c, content=<a href='/topic/show?id=5f04e51467' target=_blank style='color:#2F92EE;'>#FLT3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7514, encryptionId=5f04e51467, topicName=FLT3)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=57a713069145, createdName=fengyi816, createdTime=Sat Jun 12 01:49:43 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972851, encodeId=f3dc9e2851a7, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210610/41ac025ada93475188bc6172c56dae78/0ec9ad5bce4c43dabd50e6457b8b9e3c.jpg, createdBy=41945518358, createdName=包包123, createdTime=Fri Jun 11 14:50:43 CST 2021, time=2021-06-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=972675, encodeId=fc949e26756d, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=67634708538, createdName=1356548325, createdTime=Thu Jun 10 22:08:55 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-10 1356548325

    学习

    0

相关资讯

Blood:血液肿瘤儿童患者进行异基因造血细胞移植的有效疾病风险指数

疾病风险指数(DRI)是为接受造血干细胞移植的血液恶性肿瘤成年患者开发的,也被用来根据疾病风险对儿童和青少年患者进行分层。

Baidu
map
Baidu
map
Baidu
map