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Blood：通过去乙酰化激活LMO2对造血作用和T-ALL病的发生都必不可少

2019-08-01 MedSci MedSci原创

去乙酰化LMO2造血作用T-ALL
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LMO2(造血转录因子LIM结构域-only-2)是TAL1转录复合体的成员之一，在早期造血中发挥重要作用，常在T细胞急性淋巴细胞白血病(T-ALL)患者中激活。近期，研究人员发现LMO2是通过烟酰胺磷脂酰转移酶(NAMPT)/去乙酰化酶2 (SIRT2)通路将第74位和78位上的赖氨酸脱乙酰化来激活的。LMO2去乙酰化使LMO2与LDB1相互作用，进而激活TAL1复合物。通过去乙酰化，NAMPT

LMO2(造血转录因子LIM结构域-only-2)是TAL1转录复合体的成员之一，在早期造血中发挥重要作用，常在T细胞急性淋巴细胞白血病(T-ALL)患者中激活。近期，研究人员发现LMO2是通过烟酰胺磷脂酰转移酶(NAMPT)/去乙酰化酶2 (SIRT2)通路将第74位和78位上的赖氨酸脱乙酰化来激活的。

LMO2去乙酰化使LMO2与LDB1相互作用，进而激活TAL1复合物。通过去乙酰化，NAMPT/SIRT2介导的LMO2活化对诱导多能干细胞(iPS)的造血分化和斑马鱼胚胎的血液形成至关重要。

在T-ALL患者中，去乙酰化的LMO2可诱导TAL1复杂靶基因HHEX、NKX3.1表达，并可诱导LMO2自我调控。与此相一致，抑制NAMPT或SIRT2可通过消除LMO2的去乙酰化作用，抑制T-ALL细胞在体外生长、抑制其在体内种植。

综上所述，本研究所提出的新的分子机制或可作为T-ALL患者提供新的治疗可能，也可促进体外再生血液的技术发展。

原始出处：

Tatsuya Morishima， et al.LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis.Blood 2019 ：blood.2019000095； doi： https：//doi.org/10.1182/blood.2019000095

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    2019-08-03 膀胱癌

    #ALL#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1329264, encodeId=f5811329264c3, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, 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 Aug 03 14:28:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441318, encodeId=89da144131891, content=<a href='/topic/show?id=67311e013a7' target=_blank style='color:#2F92EE;'>#T-ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17013, encryptionId=67311e013a7, topicName=T-ALL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b6b94820128, createdName=紫砂壶, createdTime=Sat Aug 03 14:28:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1494684, encodeId=7a481494684d4, content=<a href='/topic/show?id=084d9499599' target=_blank style='color:#2F92EE;'>#造血#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=94995, encryptionId=084d9499599, topicName=造血)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=caed9138962, createdName=俅侠, createdTime=Sat Aug 03 14:28:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=370633, encodeId=a08f3e063319, content=学习学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRkia1DP5MpwEgtXo1XhXA11xD6MWKxunAZFXKSNic0fWHUQx83oNHPlRMxxIctM83QKeCLkJpMibibiaC/0, createdBy=7e581734408, createdName=深海的鱼, createdTime=Fri Aug 02 05:46:28 CST 2019, time=2019-08-02, status=1, ipAttribution=)]
    2019-08-03 紫砂壶

    #T-ALL#

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    2019-08-03 俅侠

    #造血#

    0

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    2019-08-02 深海的鱼

    学习学习学习学习

    0