title: ZFX modulates the growth of human leukemic cells via B4GALT1.
abstract: Zinc finger protein X-linked (ZFX) is a key regulator of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), which is required for both Notch intracellular domain (NotchIC)-induced acute T-cell leukemia and MLL-AF9-induced myeloid leukemia in mouse models. However, the role of ZFX and its underlying mechanism in human leukemic cells remain unclear yet, though accumulating data have demonstrated that ZFX is aberrantly expressed in various human tumors and plays an important role. Herein, we found that ZFX was aberrantly expressed in various human leukemic cell lines and primary cells from leukemia patients compared with control cells. The silence of ZFX led to the growth suppression through either the deregulated cell cycle or the induction of apoptosis in various cells including K562, Jurkat, Namalwa, and THP-1 cells. The gene expression analysis revealed that UDP-Gal:βGlcNAc β 1,4-galactosyltransferase, polypeptide 1 (B4GALT1) was significantly down-regulated upon ZFX silencing, which is implicated in the response of K562 cells to the treatment of imatinib mesylate (IM). In addition, lectin blot assay showed that the galactosylation of glycoproteins in K562 cells was suppressed upon ZFX silencing. Interestingly, overexpression of B4GALT1 restored the growth and conferred drug resistance to ZFX-silenced cells. Taken together, we have demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this 'stemness' regulator in these deadly diseases.
authors: Cyrus Tang Hematology Center , Soochow University, Suzhou 215123, China.
authors: Jie
authors: J
authors: Wu
authors: Cyrus Tang Hematology Center , Soochow University, Suzhou 215123, China.
authors: Lun
authors: L
authors: Xiao
authors: The First Affiliated Hospital, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Soochow University, Suzhou 215006, China.
authors: Haixia
authors: H
authors: Zhou
authors: The First Affiliated Hospital, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Soochow University, Suzhou 215006, China.
authors: Hong
authors: H
authors: Liu
authors: Cyrus Tang Hematology Center , Soochow University, Suzhou 215123, China.
authors: Yue
authors: Y
authors: Ge
authors: Shanghai Center for Bioinformation Technology, Shanghai 200235, China.
authors: Jing
authors: J
authors: Yang
authors: Shanghai Center for Bioinformation Technology, Shanghai 200235, China.
authors: Yuanyuan
authors: Y
authors: Li
authors: The First Affiliated Hospital, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Soochow University, Suzhou 215006, China.|The Collaborative Innovation Center of Hematology , Soochow University, Suzhou 215006, China.
authors: Depei
authors: D
authors: Wu
authors: Cyrus Tang Hematology Center , Soochow University, Suzhou 215123, China zhaoy@suda.edu.cn zhangxiuyan@suda.edu.cn.|The Collaborative Innovation Center of Hematology , Soochow University, Suzhou 215006, China.
authors: Yun
authors: Y
authors: Zhao
authors: Cyrus Tang Hematology Center , Soochow University, Suzhou 215123, China zhaoy@suda.edu.cn zhangxiuyan@suda.edu.cn.|The Collaborative Innovation Center of Hematology , Soochow University, Suzhou 215006, China.
authors: Xiuyan
authors: X
authors: Zhang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005700:Galactosyltransferases / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000473:pathology*
chemical_list: D051741:Kruppel-Like Transcription Factors; C062076:zinc finger protein, X-linked; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I
keywords: B4GALT1; ZFX; drug response; leukemia