title: Spred2 modulates the erythroid differentiation induced by imatinib in chronic myeloid leukemia cells.
abstract: 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.
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Yuefeng
authors: Y
authors: Yang
authors: Center for Disease Control and Prevention of Lanzhou Command, Lanzhou, PR China.
authors: Xiaoyun
authors: X
authors: Liu
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Fengjun
authors: F
authors: Xiao
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Shuya
authors: S
authors: Xue
authors: Department of Oncology, Qinghai Provincial People's Hospital, Xining, PR China.
authors: Qinqin
authors: Q
authors: Xu
authors: Department of Hematology, Peking University First Hospital, Beijing, PR China.
authors: Yue
authors: Y
authors: Yin
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Huiyan
authors: H
authors: Sun
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Jie
authors: J
authors: Xu
authors: Department of Hematology, General Hospital of Air Force, Beijing, PR China.
authors: Hengxiang
authors: H
authors: Wang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Qunwei
authors: Q
authors: Zhang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Hua
authors: H
authors: Wang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, PR China.
authors: Lisheng
authors: L
authors: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D041905:Erythroid Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology* / Q000627:therapeutic use; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012097:Repressor Proteins; C500760:SPRED2 protein, human; D000068877:Imatinib Mesylate