Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells.
Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells.
复制标题
Spred2 调节伊马替尼在慢性粒细胞白血病细胞中诱导的红细胞分化。
DOI：
10.1371/journal.pone.0117573
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Yang Y;Liu X;Xiao F;Xue S;Xu Q;Yin Y;Sun H;Xu J;Wang H;Zhang Q;Wang H;Wang L
诱导分化是目前治疗慢性粒细胞白血病（CML）的一种替代策略。我们的前期工作已经证实Sprouty相关EVH 1结构域蛋白2（Spread 2）参与了伊马替尼介导的CML细胞毒性。然而，其在CML细胞的生长和谱系分化中的作用仍然未知。本研究发现CML CD 34+细胞Spread 2表达水平较正常造血祖细胞低，腺病毒介导的Spread 2恢复可促进CML细胞向红系分化。伊马替尼可诱导K562细胞Spread 2表达，促进其向红系分化。然而，伊马替尼诱导的红系细胞分化可以被使用慢病毒载体PLKO.1-shSpred 2的Spred 2沉默所阻断。Spread 2干扰激活磷酸化ERK（p-ERK），抑制红系分化，而ERK抑制剂PD 98059可恢复红系分化，提示Spread 2部分通过ERK信号通路调控红系分化。此外，Spread 2干扰部分恢复p-ERK水平，导致伊马替尼处理的K562细胞中红系分化的抑制。结论：Spread 2参与CML细胞向红系分化，并部分通过ERK信号通路参与伊马替尼诱导的CML细胞向红系分化。
Differentiation induction is currently considered as an alternative strategy for treating chronic myelogenous leukemia (CML). Our previous work has demonstrated that Sprouty-related EVH1 domainprotein2 (Spred2) was involved in imatinib mediated cytotoxicity in CML cells. However, its roles in growth and lineage differentiation of CML cells remain unknown. In this study, we found that CML CD34+ cells expressed lower level of Spred2 compared with normal hematopoietic progenitor cells, and adenovirus mediated restoration of Spred2 promoted the erythroid differentiation of CML cells. Imatinib could induce Spred2 expression and enhance erythroid differentiation in K562 cells. However, the imatinib induced erythroid differentiation could be blocked by Spred2 silence using lentiviral vector PLKO.1-shSpred2. Spred2 interference activated phosphorylated-ERK (p-ERK) and inhibited erythroid differentiation, while ERK inhibitor, PD98059, could restore the erythroid differentiation, suggesting Spred2 regulated the erythroid differentiation partly through ERK signaling. Furthermore, Spred2 interference partly restored p-ERK level leading to inhibition of erythroid differentiation in imatinib treated K562 cells. In conclusion, Spred2 was involved in erythroid differentiation of CML cells and participated in imatinib induced erythroid differentiation partly through ERK signaling.
登录
查看更多内容
影响因子：
11.5
作者：
Milojkovic, Dragana;Apperley, Jane
通讯作者：
Apperley, Jane
影响因子：
64.8
作者：
Naka, Kazuhito;Hoshii, Takayuki;Hirao, Atsushi
通讯作者：
Hirao, Atsushi
影响因子：
8
作者：
Essafi, A;de Mattos, SF;Lam, EWF
通讯作者：
Lam, EWF
影响因子：
20.3
作者：
Dorsey, JF;Cunnick, JM;Wu, J
通讯作者：
Wu, J
影响因子：
6.4
作者：
Murphy, Tania;Hori, Satoshi;Gnanapragasam, Vincent J.
通讯作者：
Gnanapragasam, Vincent J.