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.
Highlights
Chronic myelogenous leukemia (CML) arises mostly from a pluripotent hematopoietic stem cell that contains thereciprocal t(9;22)(q34;q11) chromosomal translocation coding BCR/ABL fusion oncoprotein
To clarify the roles of Sprouty-related EVH1 domainprotein2 (Spred2) in erythroid differentiation of normal hematopoietic stem/progenitor cells, the NBM CD34+ cells were transduced with PLKO.1-shSpred2, a lentivirus vector with shRNA targeting Spred2 (Fig. 1A–1B), or PLKO.1-shScramble
Spred2 was involved in imatinib induced erythroid differentiation of K562 cells
Summary
Chronic myelogenous leukemia (CML) arises mostly from a pluripotent hematopoietic stem cell that contains thereciprocal t(9;22)(q34;q11) chromosomal translocation coding BCR/ABL fusion oncoprotein. Clinical resistance to these drugs has been widely reported in CML patients [6,7,8,9].
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