文章：

Ropeginterferon alpha-2b 在体外和体内靶向作用于JAK2V617F阳性的真性红细胞增多症细胞

Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo

原文发布日期：2018-10-04

DOI: 10.1038/s41408-018-0133-0

类型: Article

开放获取: 是

英文摘要：

Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation. Recommended treatments include hydroxyurea and interferon-alpha. Several groups have reported a reduction in the JAK2 mutant allele burden in interferon-treated patients, but significance of this observation is questioned. We characterized the activity of ropeginterferon alpha-2b, a novel form of interferon-alpha recently shown to be safe and efficacious in polycythemia vera. Ropeginterferon was able to inhibit the proliferation of the HEL, UKE-1, and UT-7 JAK2-mutant cell lines while sparing JAK2-wild-type UT-7 and normal CD34+ cells growth. In vitro treatment of erythroid progenitors derived from PV patients showed that ropeginterferon could considerably inhibit the growth of endogenous erythroid colonies, a hallmark of polycythemia vera. Finally, we could study in sequential samples the clonal architecture of erythroid progenitors derived from patients included in a randomized study comparing hydroxyurea to ropeginterferon. After 1 year of treatment with ropeginterferon, the ratio of JAK2-mutated to wild-type colonies grown from bone marrow progenitors was reduced by 64%, compared to 25% in patients receiving hydroxyurea. This study shows that ropeginterferon has a potent targeted activity against JAK2-mutant cells and is able to drastically reduce the proportion of malignant progenitors in patients treated with this drug.

摘要翻译： 

真性红细胞增多症的特征是获得JAK2V617F突变。推荐治疗包括羟基脲和α-干扰素。多个研究组报告了干扰素治疗患者JAK2突变等位基因负荷的减少，但这一观察的意义受到质疑。我们研究了罗培干扰素α-2b（一种近期被证明在真性红细胞增多症中安全有效的新型α-干扰素）的活性。罗培干扰素能够抑制HEL、UKE-1和UT-7 JAK2突变细胞系的增殖，同时不影响JAK2野生型UT-7细胞和正常CD34+细胞的生长。对真红患者来源的红系祖细胞进行体外处理显示，罗培干扰素能显著抑制内源性红系集落（真性红细胞增多症的标志性特征）的生长。最后，我们通过系列样本研究了来自一项比较羟基脲与罗培干扰素的随机研究患者的红系祖细胞克隆结构。经罗培干扰素治疗1年后，骨髓祖细胞生长的JAK2突变与野生型集落比例降低了64%，而接受羟基脲治疗的患者仅降低25%。本研究表明罗培干扰素对JAK2突变细胞具有强效靶向活性，并能显著降低接受该药物治疗患者的恶性祖细胞比例。

原文链接：

Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo