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Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia
Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215003, Jiangsu, China
Department of Gastroenterology, the 5th Hospital of Chinese PLA, Yinchuan 750004, Ningxia, China
Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing100021, China
Translational Research Center, The Second Clinical School, Nanjing Medical University, Nanjing 210011, Jiangsu, China
* Author to whom correspondence should be addressed.
Received: 21 November 2012; in revised form: 29 January 2013 / Accepted: 30 January 2013 / Published: 6 February 2013
Abstract: Histone modification enzymes regulate gene expression by altering the accessibility of promoters to transcription factors. We sought to determine whether the genes encoding histone modification enzymes are dysregulated in pediatric acute lymphoblastic leukemia (ALL). A real-time PCR array was designed, tested and used to profile the expression of 85 genes encoding histone modification enzymes in bone marrow mononuclear cells from 30 pediatric ALL patients and 20 normal controls. The expression profile of histone-modifying genes was significantly different between normal karyotype B cell pediatric ALL and normal controls. Eleven genes were upregulated in pediatric ALL, including the histone deacetylases HDAC2 and PAK1, and seven genes were downregulated, including PRMT2 and the putative tumor suppressor EP300. Future studies will seek to determine whether these genes serve as biomarkers of pediatric ALL. Ingenuity Pathway Analysis revealed that Gene Expression and Organ Morphology was the highest rated network, with 13 focus molecules (significance score = 35). Ingenuity Pathway Analysis also indicated that curcumin and miR-34 are upstream regulators of histone-modifying enzymes; future studies will seek to validate these results and examine the role of curcumin and miR-34 in leukemia. This study provides new clues into the molecular mechanisms of pediatric ALL.
Keywords: histone-modifying enzymes; pediatric acute lymphoblastic leukemia; real-time PCR array
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Tao, Y.-F.; Pang, L.; Du, X.-J.; Sun, L.-C.; Hu, S.-Y.; Lu, J.; Cao, L.; Zhao, W.-L.; Feng, X.; Wang, J.; Wu, D.; Wang, N.; Ni, J.; Pan, J. Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia. Int. J. Mol. Sci. 2013, 14, 3376-3394.
Tao Y-F, Pang L, Du X-J, Sun L-C, Hu S-Y, Lu J, Cao L, Zhao W-L, Feng X, Wang J, Wu D, Wang N, Ni J, Pan J. Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences. 2013; 14(2):3376-3394.
Tao, Yan-Fang; Pang, Li; Du, Xiao-Juan; Sun, Li-Chao; Hu, Shao-Yan; Lu, Jun; Cao, Lan; Zhao, Wen-Li; Feng, Xing; Wang, Jian; Wu, Dong; Wang, Na; Ni, Jian; Pan, Jian. 2013. "Differential mRNA Expression Levels of Human Histone-Modifying Enzymes in Normal Karyotype B Cell Pediatric Acute Lymphoblastic Leukemia." Int. J. Mol. Sci. 14, no. 2: 3376-3394.