The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0-91 cell lines harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.

译文

首先通过克隆先天性纤维肉瘤 (CFS) 中的t(12;15)(p13;q25) 易位来鉴定编码嵌合酪氨酸激酶的ETV6-NTRK3 (EN) 融合基因。此后,在先天性中胚层肾瘤 (CMN),分泌性乳腺癌 (SBC) 和急性骨髓性白血病 (AML) 中也发现了EN。使用带有EN融合基因的IMS-M2和M0-91细胞系以及用EN稳定转染的Ba/F3细胞,我们证明了PKC412 (也称为midostaurin) 是EN的抑制剂。PKC412对EN活性的抑制抑制了其下游分子的活性,从而抑制了细胞增殖并诱导了凋亡。我们的数据首次表明PKC412可以作为治疗这种融合患者的治疗药物。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录