Comparative Epigenetics Analyses of Acute and Chronic Leukemia

Zhang Yan, Dianjing Guo

School of Life Sciences and the State Key Laboratory of Agribiotechnolgy, The Chinese University of Hong Kong, Hong Kong, China.

DOI: 10.4236/jbm.2015.37002                

Abstract

Comparative analysis of epigenetic alterations between acute and chronic leukemia, with an emphasis on histone modifications, was conducted. We focused on the promoter regions of the whole genomes as well as oncogenes. Our results revealed that obvious differential histone modifications pattern existed between the two subtypes. H3K27ac had a high tag density in the promoter region in both Dnd41 cell lines and K562 cell lines. H3K27ac and H3K4me1 had high correlation between the two cell lines of oncogenes. Similar results were also achieved in the promoter region of high expression genes in the Jurkat and K562 cell lines based on RNA-seq data. This suggested that H2K27ac and H3K4me1 were active regulators in leukemia cell lines.

Keywords

Leukemia, Epigenetics, Histone Modification, Promoter

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition, World Health Organization, Lyon.
[2]	Chiorazzi, N., Rai, K.R. and Ferrarini, M. (2005) Chronic Lymphocytic Leukemia. The New England Journal of Medicine, 352, 804-815. http://dx.doi.org/10.1056/NEJMra041720
[3]	Dighiero, G., Travade, P., Chevret, S., Fenaux, P., Chastang, C. and Binet, J.L. (1991) B-Cell Chronic Lymphocytic Leukemia: Present Status and Future Directions. French Cooperative Group on CLL. Blood, 78, 1901-1914.
[4]	Rawstron, A.C. (2009) Monoclonal B-Cell Lymphocytosis. ASH Education Book, 2009, 430-439. http://dx.doi.org/10.1182/asheducation-2009.1.430
[5]	Rossi, D., Sozzi, E., Puma, A., De Paoli, L., Rasi, S., Spina, V., et al. (2009) The Prognosis of Clinical Monoclonal B Cell Lymphocytosis Differs from Prognosis of Rai 0 Chronic Lymphocytic Leukaemia and Is Recapitulated by Biological Risk Factors. British Journal of Haematology, 146, 64-75. http://dx.doi.org/10.1111/j.1365-2141.2009.07711.x
[6]	Shanafelt, T.D., Kay, N.E., Rabe, K.G., Call, T.G., Zent, C.S., Maddocks, K., et al. (2009) Natural History of Individuals with Clinically Recognized Monoclonal B-Cell Lymphocytosis Compared with Patients with Rai 0 Chronic Lymphocytic Leukemia. Journal of Clinical Oncology, 27, 3959-3963. http://dx.doi.org/10.1200/JCO.2008.21.2704
[7]	Zenz, T., Gribben, J.G., Hallek, M., Döhner, H., Keating, M.J. and Stilgenbauer, S. (2012) Risk Categories and Refractory CLL in the Era of Chemoimmunotherapy. Blood, 119, 4101-4107. http://dx.doi.org/10.1182/blood-2011-11-312421
[8]	Zenz, T., Mertens, D., Küppers, R., Döhner, H. and Stilgenbauer, S. (2010) From Pathogenesis to Treatment of Chronic Lymphocytic Leukaemia. Nature Reviews Cancer, 10, 37-50. http://dx.doi.org/10.1038/nrc2764
[9]	Skinner, M.K., Manikkam, M. and Guerrero-Bosagna, C. (2010) Epigenetic Transgenerational Actions of Environmental Factors in Disease Etiology. Trends in Endocrinology & Metabolism, 21, 214-222. http://dx.doi.org/10.1016/j.tem.2009.12.007
[10]	Doherty, R., Farrelly, C.O. and Meade, K.G. (2014) Comparative Epigenetics: Relevance to the Regulation of Production and Health Traits in Cattle. Animal Genetics, 45, 3-14. http://dx.doi.org/10.1111/age.12140
[11]	Bhat, A.A., Wani, H.A., Beigh, M.A., Bhat, S.A., Jeelani, S., Massood, A., et al. (2013) Epigenetic Promoter Methylation of Hmlh1 Gene in Human Gut Malignancies: A Comparative Study. Journal of Investigational Biochemistry, 2, 101-108. http://dx.doi.org/10.5455/jib.20130409124009
[12]	Feinberg, A.P. and Tycko, B. (2004) The History of Cancer Epigenetics. Nature Reviews Cancer, 4, 143-153. http://dx.doi.org/10.1038/nrc1279
[13]	Deakin, J.E., Domaschenz, R., Lim, P.S., Ezaz, T. and Rao, S. (2014) Comparative Epigenomics: An Emerging Field with Breakthrough Potential to Understand Evolution of Epigenetic Regulation. AIMS Genetics, 1, 34-54. http://dx.doi.org/10.3934/genet.2014.1.34
[14]	Henrique, R., Luis, A. and Jerónimo, C. (2012) The Epigenetics of Renal Cell Tumors: From Biology to Biomarkers. Frontiers in Genetics, 3, 94. http://dx.doi.org/10.3389/fgene.2012.00094
[15]	Shi, Y. (2007) Histone Lysine Demethylases: Emerging Roles in Development, Physiology and Disease. Nature Reviews Genetics, 8, 829-833. http://dx.doi.org/10.1038/nrg2218
[16]	Kouzarides, T. (2007) Chromatin Modifications and Their Function. Cell, 128, 693-705. http://dx.doi.org/10.1016/j.cell.2007.02.005
[17]	Fraga, M.F., Ballestar, E., Villar-Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., et al. (2005) Loss of Acetylation at Lys16 and Trimethylation at Lys20 of Histone H4 Is a Common Hallmark of Human Cancer. Nature Genetics, 37, 391-400. http://dx.doi.org/10.1038/ng1531
[18]	Nguyen, C.T., Weisenberger, D.J., Velicescu, M., Gonzales, F.A., Lin, J.C., Liang, G., et al. (2002) Histone H3-Lysine 9 Methylation Is Associated with Aberrant Gene Silencing in Cancer Cells and Is Rapidly Reversed by 5-Aza-2’- deoxycytidine. Cancer Research, 62, 6456-6461.
[19]	Langmead, B. and Salzberg, S.L. (2012) Fast Gapped-Read Alignment with Bowtie 2. Nature Methods, 9, 357-359. http://dx.doi.org/10.1038/nmeth.1923
[20]	Wang, L., Feng, Z., Wang, X., Wang, X. and Zhang, X. (2010) DEGseq: An R Package for Identifying Differentially Expressed Genes from RNA-Seq Data. Bioinformatics, 26, 136-138. http://dx.doi.org/10.1093/bioinformatics/btp612
[21]	Pruitt, K.D., Tatusova, T. and Maglott, D.R. (2007) NCBI Reference Sequences (RefSeq): A Curated Non-Redundant Sequence Database of Genomes, Transcripts and Proteins. Nucleic Acids Research, 35, D61-D65. http://dx.doi.org/10.1093/nar/gkl842
[22]	Xu, H., Wei, C.-L., Lin, F. and Sung, W.-K. (2008) An HMM Approach to Genome-Wide Identification of Differential Histone Modification Sites from ChIP-Seq Data. Bioinformatics, 24, 2344-2349. http://dx.doi.org/10.1093/bioinformatics/btn402