Expression of zinc finger protein X-linked in childhood B lineage acute lymphoblastic leukemia
WANG Zhuo, LIANG Huan-Huan, LI Ben-Shang, HUANG Xiao-Hang, ZHANG Jing, WANG Xiang, DING Li-Xia, JIANG Hua
Department of Hematology and Oncology, Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China. jiang_hua18@sina.cn
Abstract：OBJECTIVE: To study the expression of zinc finger protein X-linked (ZFX) in bone marrow mononuclear cells (BMMCs) of children with B lineage acute lymphoblastic leukemia (B-ALL) and its relationship with prognosis. METHODS: The expression of ZFX in human leukemia cell lines (REH, HL-60, NB4 and K562) was measured by Western blot. ZFX gene was cloned by PCR from one patient and DNA sequencing technology was used to confirm it. Real-time PCR was used for detecting ZFX mRNA expression in the BMMCs of 82 children with newly-diagnosed B-ALL, 24 children with complete remission (CR) after induction therapy and 64 control children (fracture or congenital heart disease patients). According to the presence of bone marrow or central nervous system relapse during a follow-up of 3 years, the patients were identified as having a good or poor prognosis. Their ZFX mRNA levels in BMMCs at diagnosis were compared. RESULTS: ZFX protein was expressed in human leukemia cell lines REH, HL-60, NB4 and K562. ZFX mRNA expression was significantly higher in the newly-diagnosed ALL group than in the control group (P＜0.01). ZFX mRNA expression in the ALL CR group was significantly reduced compared with the newly-diagnosed ALL group (P＜0.01). Children with a poor prognosis had significantly higher ZFX mRNA levels at diagnosis than those with a good prognosis (P＜0.05). CONCLUSIONS: ZFX is over-expressed in children with B-ALL and its levels are higher in those with a poor prognosis than those with a good prognosis, which suggests that ZFX is important in the prognosis evaluation of B-ALL.
WANG Zhuo,LIANG Huan-Huan,LI Ben-Shang et al. Expression of zinc finger protein X-linked in childhood B lineage acute lymphoblastic leukemia[J]. CJCP, 2013, 15(7): 509-513.
［2］Schneider GA, Beer RP, Brown LG. Putative transcription activator with alternative isoforms encoded by human ZFX gene［J］. Nature, 1989, 342(6250): 708-711.
［3］Galan-Caridad JM, Harel S, Arenzana TL, Esther Hou Z, Doetsch FK, Mirny LA, et al. Zfx controls the self-renewal of embryonic and hematopoietic stem cells［J］. Cell, 2007, 129(2): 345-357.
［4］Jiang H, Zhang L, Liu J, Chen Z, Na R, Ding G, et al. Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9［J］. Cancer Gene Ther, 2012, 19(10): 684-689.
［19］Arenzana TL, Smith-Raska MR, Reizis B. Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes［J］. Blood, 2009, 113 (23): 5857-5867.
［5］Fang J, Yu Z, Lian M, Ma H, Tai J, Zhang L, et al. Knockdown of zinc finger protein, X-linked (ZFX) inhibits cell proliferation and induces apoptosis in human laryngeal squamous cell carcinoma［J］. Mol Cell Biochem, 2012, 360(1-2): 301-307.
Zhou Y, Su Z, Huang Y, Sun T, Chen S, Wu T, et al. The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251[J]. J Exp Clin Cancer Res, 2011, 30: 114. doi: 10.1186/1756-9966-30-114.
［7］Nikpour P, Emadi-Baygi M, Mohammad-Hashem F, Maracy MR, Haghjooy-Javanmard S. Differential expression of ZFX gene in gastric cancer［J］. J Biosci, 2012, 37(1): 85-90.
［20］Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors［J］. Oncogene, 2004, 23 (43): 7267-7273.
［8］Sakhinia E, Glennie C, Hoyland JA, Menasce LP, Brady G, Miller C, et al. Clinical quantitation of diagnostic and predictive gene expression levels in follicular and diffuse large B-cell lymphoma by RT-PCR gene expression profiling［J］. Blood, 2007, 109(9): 3922-3928.
［9］Saha MN, Jiang H, Mukai A, Chang H. RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlininduced cytotoxic responses［J］. Mol Cancer Ther, 2010, 9(11): 3041-3051.
［10］Wang Z, Cao L, Kang R, Yang M, Liu L, Zhao Y, et al. Autophagy regulates myeloid cell differentiation by p62/SQSTM1-mediated degradation of PML-RARα oncoprotein［J］. Autophagy, 2011, 7(4): 401-411.
［12］Chandrasekharan S, Kumar S, Valley CM, Rai A. Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins［J］. Nat Biotechnol, 2009, 27(2): 140-144.
［13］Schnidar H, Eberl M, Klingler S, Mangelberger D, Kasper M, Hauser-Kronberqer C, et al. Epidermal growth factor receptor signaling synergizes with Hedgehog/GLI in oncogenic transformation via activation of the MEK/ERK/JUN pathway［J］. Cancer Res, 2009, 69(4): 1284-1292.
［14］Hu G, Kim J, Xu Q, Leng Y, Orkin SH, Elledge SJ. A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal［J］. Genes Dev, 2009, 23(7): 837-848.
［15］Schneider-Gadicke A, Beer-Romero P, Brown LG, Nussbaum R, Page DC. ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation［J］. Cell, 1989, 57(7): 1247-1258.
［16］Cellot S, Sauvageau G. Zfx: at the crossroads of survival and self-renewal［J］. Cell, 2007, 129(2): 239-241.
［17］Ivanova N, Dobrin R, Lu R, Kotenko I, Levorse J, DeCoste C, et al. Dissecting self-renewal in stem cells with RNA interference［J］. Nature, 2006, 442(7102): 533-538.
［18］Matoba R, Niwa H, Masui S, Ohtsuka S, Carter MG, Sharov AA, et al. Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling［J］. PLoS ONE, 2006, 20(1): e26.
［19］Arenzana TL, Smith-Raska MR, Reizis B. Transcription factor Zfx controls BCR-induced proliferation and survival of B lymphocytes［J］. Blood, 2009, 113 (23): 5857-5867.
［20］Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors［J］. Oncogene, 2004, 23 (43): 7267-7273.
