期刊
FASEB JOURNAL
卷 32, 期 2, 页码 681-692出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201700690R
关键词
nucleus; erythropoiesis; lenalidomide; chromosome 5q deletion
资金
- Italian Ministero dell'Istruzione dell'Universita e della Ricerca-Progetti di Ricerca di Interesse Nazionale
- Intesa S. Paolo
PI-PLC beta 1 is involved in cell proliferation, differentiation, and myelodysplastic syndrome (MDS) pathogenesis. Moreover, the increased activity of PI-PLC beta 1 reduces the expression of PKC-alpha, which, in turn, delays the cell proliferation and is linked to erythropoiesis. Lenalidomide is currently used in low-risk patients with MDS and del(5q), where it can suppress the del(5q) clone and restore normal erythropoiesis. In this study, we analyzed the effect of lenalidomide on 16 patients with low-risk del(5q) MDS, as well as del(5q) and non-del(5q) hematopoietic cell lines, mainly focusing on erythropoiesis, cell cycle, and PI-PLC beta 1/PKC-alpha signaling. Overall, 11 patients were evaluated clinically, and 10 (90%) had favorable responses; the remaining case had a stable disease. At a molecular level, both responder patients and del(5q) cells showed a specific induction of erythropoiesis, with a reduced gamma/beta-globin ratio, an increase in glycophorin A, and a nuclear translocation of PKC-alpha. Moreover, lenalidomide could induce a selective G(0)/G(1) arrest of the cell cycle in del(5q) cells, slowing down the rate proliferation in those cells. Altogether, our results could not only better explain the role of PI-PLC beta 1/PKC-alpha signaling in erythropoiesis but also lead to a better comprehension of the lenalidomide effect on del(5q) MDS and pave the way to innovative, targeted therapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据