ZFX modulates the growth of human leukemic cells via B4GALT1  

作　　者：Jie Wu Lun Xiao Haixia Zhou Hong Liu Yue Ge Jing Yang Yuanyuan Li Depei Wu Yun Zhao Xiuyan Zhang 

机构地区：[1]Cyrus Tang Hematology Center, Soochow University, Suzhou 215123, China [2]The First Affiliated Hospital, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Soochow University, Suzhou 215006, China [3]The Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China [4]Shanghai Center for Bioinformation Technology, Shanghai 200235, China

出　　处：《Acta Biochimica et Biophysica Sinica》2016年第12期1120-1127,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （Nos. 81500119, 81270617, and 31371392）, the National Key Scientific Project of China （973 Program） （No. 2011CB933501）, the National High-tech R＆D Program （863 Program） （No. 2012AA02A505）, Jiangsu Province＇s Key Medical Center （No. ZX201102）, the National Public Health Grand Research Foundation （No. 201202017）, and the Priority Academic Program Development of Jiangsu Higher Education Institutions （PAPD）.

摘　　要：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 （NotchlC）- 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-GaI：βGIcNAc β 1,4-galactosyltransferase, polypeptide 1 （B4GALT1） was significantly down-regulated upon ZFX silencing, which is impli- cated 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.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 （NotchlC）- 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-GaI：βGIcNAc β 1,4-galactosyltransferase, polypeptide 1 （B4GALT1） was significantly down-regulated upon ZFX silencing, which is impli- cated 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.

关 键 词：ZFX LEUKEMIA B4GALT1 drug response 

分 类 号：Q71[生物学—分子生物学] X503.231[环境科学与工程—环境工程]