Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells.
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4331423?pdf=render |
| _version_ | 1818366129167400960 |
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| author | Yuefeng Yang Xiaoyun Liu Fengjun Xiao Shuya Xue Qinqin Xu Yue Yin Huiyan Sun Jie Xu Hengxiang Wang Qunwei Zhang Hua Wang Lisheng Wang |
| author_facet | Yuefeng Yang Xiaoyun Liu Fengjun Xiao Shuya Xue Qinqin Xu Yue Yin Huiyan Sun Jie Xu Hengxiang Wang Qunwei Zhang Hua Wang Lisheng Wang |
| author_sort | Yuefeng Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T22:31:15Z |
| format | Article |
| id | doaj.art-84a0cdf7951b4ac9b24eb3b41654831a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T22:31:15Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-84a0cdf7951b4ac9b24eb3b41654831a2022-12-21T23:29:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011757310.1371/journal.pone.0117573Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells.Yuefeng YangXiaoyun LiuFengjun XiaoShuya XueQinqin XuYue YinHuiyan SunJie XuHengxiang WangQunwei ZhangHua WangLisheng WangDifferentiation 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.http://europepmc.org/articles/PMC4331423?pdf=render |
| spellingShingle | Yuefeng Yang Xiaoyun Liu Fengjun Xiao Shuya Xue Qinqin Xu Yue Yin Huiyan Sun Jie Xu Hengxiang Wang Qunwei Zhang Hua Wang Lisheng Wang Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. PLoS ONE |
| title | Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. |
| title_full | Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. |
| title_fullStr | Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. |
| title_full_unstemmed | Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. |
| title_short | Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells. |
| title_sort | spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells |
| url | http://europepmc.org/articles/PMC4331423?pdf=render |
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