Blood：特殊血癌疗法的新靶点

  来自约克大学等处的研究人员近日鉴别出了一种新型的治疗靶点，其或许可以帮助开发治疗名为骨髓增生性肿瘤(Myeloproliferative neoplasms，MPNs)的特殊血癌的新型疗法，相关研究刊登于国际杂志Blood上。
  红细胞通常会为机体组织和血小板携带氧气，血小板主要负责凝血及阻断组织出血等；机体组织循环血细胞的严格控制对于机体健康至关重要，但在大多数MPN患者机体中，蛋白质JAK2的突变会致使血细胞快速增殖。
  文章中研究人员Ian Hitchcock表示，蛋白分子Mpl可以接收来自细胞外的化学信号，其对于突变JAK2疾病的发生是必须的；利用实验室模型进行研究，我们发现关闭Mpl受体的一半基因可以减少其表达，进而抑制JAK2疾病的发生。
  本文研究对于医学研究非常重要，因为研究结果意味着我们可以靶向作用Mpl分子，如果可以干扰其活性或许就可以帮助我们开发治疗疾病的新型疗法；与此同时研究者发现去除Mpl整个受体并不必须，仅仅降低其表达就会对个体骨髓增生性肿瘤的发生具有明显的抑制效应。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm
Blood doi:10.1182/blood-2014-07-587238
Veena Sangkhae1, S. Leah Etheridge2, Kenneth Kaushansky1, and Ian S. Hitchcock3,*
The most frequent contributing factor in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is the acquisition of a V617F mutation in Janus kinase 2 (JAK2) in hematopoietic stem cells (HSCs). Recent evidence has demonstrated that to drive MPN transformation, JAK2V617F needs to directly associate with a functional homodimeric type I cytokine receptor, suggesting that although acquiring JAK2V617F may promote disease, there are additional cellular components necessary for MPN development. Here we show that loss of the thrombopoietin (TPO) receptor (MPL) significantly ameliorates MPN development in JAK2V617F+ transgenic mice, while loss of TPO only mildly affects the disease phenotype. Specifically, when compared to JAK2V617F+ mice, JAK2V617F+Mpl-/- mice exhibited reduced thrombocythemia, neutrophilia, splenomegaly and neoplastic stem cell pool. The importance of MPL is highlighted as JAK2V617FMpl+/- mice displayed a significantly reduced MPN phenotype, indicating that Mpl level may have a substantial effect on MPN development and severity. Splenomegaly and the increased neoplastic stem cell pool were retained in JAK2V617F+Tpo-/- mice although thrombocytosis was reduced compared to JAK2V617F+ mice. These results demonstrate that Mpl expression, but not Tpo, is fundamental in the development of JAK2V617F+ MPNs, highlighting an entirely novel target for therapeutic intervention.