Recent advances in molecular pathogenesis of myeloproliferative neoplasms
Recent advances in molecular pathogenesis of myeloproliferative neoplasms
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骨髓增生性肿瘤分子发病机制的最新进展
DOI：
10.11406/rinketsu.57.156
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
池田和彦
中科院分区：
文献类型：
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作者：
Nakano H;Fujiwara SI;Ito S;Mashima K;Umino K;Minakata D;Yamasaki R;Kawasaki Y;Sugimoto M;Ashizawa M;Yamamoto C;Hatano K;Okazuka K;Sato K;Oh I;Ohmine K;Suzuki T;Muroi K;Kanda Y;池田和彦
骨髓增生性肿瘤(MPN)的特征是JAK-STAT通路被激活，这是由于JAK2V617F和MPLW515K/L等驱动程序突变以及CALRCALR突变所致。驱动突变使多个STAT蛋白磷酸化，从而导致各种造血细胞的增殖、分化和细胞因子分泌。然而，携带JAK2V617F的造血细胞会导致细胞过度增殖和分化，在造血再繁殖方面并不一定具有克隆生长优势。涉及组蛋白修饰和DNA甲基化的表观遗传修饰物的改变，通常与驱动突变共存，最终上调几个癌基因，可能在以进展为MPN的骨髓纤维化或急性白血病为特征的长期临床过程中发挥关键作用。除了JAK2抑制外，表观遗传异常修饰改变的分子可能是MPNS潜在的新的治疗靶点。
Myeloproliferative neoplasms (MPNs) are characterized by activation of the JAK-STAT pathway due to driver mutations including JAK2V617F and MPLW515K/L, as well as to mutations in CALR. Driver mutations phosphorylate multiple STAT proteins that lead to proliferations, differentiations and cytokine secretions of various hematopoietic cells. However, hematopoietic cells carrying JAK2V617F, which causes excessive cellular proliferation and differentiation, do not necessarily have a clonal growth advantage in terms of hematopoietic repopulation. Alterations of epigenetic modifiers involving histone modifications and DNA methylations, which often co-exist with driver mutations and eventually upregulate several oncogenes, may play crucial roles in long-term clinical courses characterized by progression to myelofibrosis or acute leukemia in MPNs. In addition to JAK2 inhibition, molecules altered by abnormal epigenetic modifications may be worth exploring as potential new therapeutic targets in MPNs.