Regulatory network of GATA3 in pediatric acute lymphoblastic leukemia
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Qianqian Hou1,*, Fei Liao1,*, Shouyue Zhang1,*, Duyu Zhang1,*, Yan Zhang2, Xueyan Zhou1, Xuyang Xia1, Yuanxin Ye8, Hanshuo Yang3, Zhaozhi Li1, Leiming Wang4, Xi Wang5, Zhigui Ma6, Yiping Zhu6, Liang Ouyang3, Yuelan Wang1, Hui Zhang7, Li Yang3, Heng Xu1,8, Yang Shu1
1Department of Laboratory Medicine, Precision Medicine Center, State Key Laboratory of Biotherapy and Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China
2Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
3State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China
4Department of Molecular Biology, Baylor College of Medicine, Houston, Texas, USA
5Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angles, Los Angles, California, USA
6Department of Pediatric Hematology/Oncology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
7Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA
8Department of Laboratory Medicine, Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
*These authors contributed equally to this work
Heng Xu, email: firstname.lastname@example.org
Yang Shu, email: email@example.com
Keywords: GATA3, acute lymphoblastic leukemia, tissue-specific regulation network, microarray datasets
Received: February 21, 2017 Accepted: March 11, 2017 Published: March 21, 2017
GATA3 polymorphisms were reported to be significantly associated with susceptibility of pediatric B-lineage acute lymphoblastic leukemia (ALL), by impacting on GATA3 expression. We noticed that ALL-related GATA3 polymorphism located around in the tissue-specific enhancer, and significantly associated with GATA3 expression. Although the regulatory network of GATA3 has been well reported in T cells, the functional status of GATA3 is poorly understood in B-ALL. We thus conducted genome-wide gene expression association analyses to reveal expression associated genes and pathways in nine independent B-ALL patient cohorts. In B-ALL patients, 173 candidates were identified to be significantly associated with GATA3 expression, including some reported GATA3-related genes (e.g., ITM2A) and well-known tumor-related genes (e.g., STAT4). Some of the candidates exhibit tissue-specific and subtype-specific association with GATA3. Through overexpression and down-regulation of GATA3 in leukemia cell lines, several reported and novel GATA3 regulated genes were validated. Moreover, association of GATA3 expression and its targets can be impacted by SNPs (e.g., rs4894953), which locate in the potential GATA3 binding motif. Our findings suggest that GATA3 may be involved in multiple tumor-related pathways (e.g., STAT/JAK pathway) in B-ALL to impact leukemogenesis through epigenetic regulation.
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