Blood：CDK9是成人T细胞白血病/淋巴瘤的一种新的特异性分子靶点

2017-06-29 xiaoxiao MedSci原创

成人T细胞白血病/淋巴瘤 (adult T-cell leukemia/lymphoma，ATL)是周围性T细胞淋巴瘤的一种特殊类型 ,早在1976年 ,由日本高月清教授首先提出 ,它是由人T细胞白血病毒 (human T cell leukemialymphoma virus- 1,HTL V- 1)感染引起的一种高度白血病样的疾病。细胞周期蛋白依赖性激酶9（Cyclin-dependent k

成人T细胞白血病/淋巴瘤 (adult T-cell leukemia/lymphoma，ATL)是周围性T细胞淋巴瘤的一种特殊类型 ,早在1976年 ,由日本高月清教授首先提出 ,它是由人T细胞白血病毒 (human T cell leukemialymphoma virus- 1,HTL V- 1)感染引起的一种高度白血病样的疾病。

细胞周期蛋白依赖性激酶9（Cyclin-dependent kinase 9 ，CDK9），是正转录延伸因子B（the positive transcription elongation factor b，P-TEFb）复合物的一个亚基，通过RNA聚合酶II（RNAPII）的羧基末端结构域（CTD）的磷酸化调节基因的转录延伸。CDK9/P-TEFb的异常表达对许多类型的癌症的有着重要意义。BAY1143572是一种高选择性的新型CDK9/P-TEFb抑制剂，该药目前正处在研究的第一阶段。

研究人员评价了BAY1143572对成人T细胞白血病/淋巴瘤的治疗潜力。在对CDK9抑制作用和随后对RNAPII CTD的丝氨酸2磷酸化的抑制作用方面，BAY1143572降低ALT衍生或HTLV-1转化的c-Myc和Mcl-1水平降低原发性ATL细胞水平，导致其生长抑制和凋亡。BAY1143572的对ALT衍生细胞或HTLV-1转化细胞（n=8）、原发性ATL细胞（n=11）和来自健康志愿者的CD4阳性细胞（n=5）的半数抑制浓度（IC50）分别为0.535、0.30、0.36µm。

同时，研究人员使用NOG小鼠作为肿瘤细胞（来自ATL患者）受体。与未治疗组（n=8）相比，BAY1143572治疗ATL小鼠（每日一次，12.5mg/kg，口服；n=8），表现出肝脏和骨髓中ATL细胞浸润显著降低，以及人体血清中可溶性白细胞介素-2受体水平（反映ATL肿瘤负担）的降低。与未经治疗的ATL小鼠相比，BAY1143572治疗后，ATL小鼠的生存期显著延长。

总而言之，本研究表明，BAY1143572显示出强大的潜力作为一种新的ATL治疗药物。

原始出处：

Narita T, Ishida T,et al.Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma.Blood. 2017 Jun 23. pii: blood-2016-09-741983. doi: 10.1182/blood-2016-09-741983. [Epub ahead of print]

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2018-06-13 jinweidong

#特异性#

51 0
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2017-07-01 zhouqu_8

#CDK#

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2017-06-30 执着追梦

学习，谢谢分享

69 0
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2017-06-30 明月清辉

谢谢分享，学习了

61 0
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2017-06-30 龙胆草

学习谢谢分享

61 0
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2017-06-30 刘煜

学习了谢谢分享

61 0
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2017-06-30 1e145228m78(暂无匿称)

学习了，谢谢作者分享!

74 0
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2017-06-30 忠诚向上

好好的学习一下

27 0
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2017-06-30 ren1mw

学习一下吧！学习

41 0
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2017-06-30 明心见性

学习了，谢谢分享

30 0