Ensive analysis supports the concept Marimastat that the epigenetic changes along with the altered expression of genes have the potential to predict clinical outcome in early stage CLL patients. Keywords: Promoter methylation, PAX9, Circadian rhythm, Transcription factors* Correspondence: drritugupta@gmail.com; drritu.laboncology@aiims.edu 1 Laboratory Oncology Unit, Dr. B.R.A.IRCH, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India Full list of author information is available at the end of the article?The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Rani et al. Clinical Epigenetics (2017) 9:Page 2 ofBackground Chronic lymphocytic leukemia (CLL) arises from a malignant clone of B cells due to altered control of apoptosis and dysregulated rate PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3081428 of proliferation. Its progression is characterized by clonal proliferation and accumulation of mature neoplastic CD5+ B lymphocytes [1]. The clinical course of CLL patients is extremely variable with some patients progressing rapidly as compared to others and ultimately, requiring therapeutic intervention. Several biomarkers including immunoglobulin PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16474207 heavy chain variable (IGHV) gene mutations that segregate CLL patients into low and high-risk clinical groups are widely used to assess the prognosis of these patients. Low-risk patients generally display mutated IGHV gene, low CD38, and low chain associated protein kinase-70 (ZAP-70) expression, while high-risk cases exhibit the reverse pattern [2?]. Altered DNA methylation is one of the hallmark events in cancer. The first evidence of DNA methylation in CLL was presented by Wahlfors et al. [7] in which a global loss of methylation was reported. In addition to global hypomethylation, hypermethylation of individual gene promoters has also been reported in CLL [7?1]. Methylation of TWIST2 and ZAP-70 exhibited a strong association with the IGHV-mutated status [9, 12] whereas methylation of HOXA4 gene was predominantly associated with the IGHV unmutated status [13]. Further studies employing genome wide methylation profiling technologies have revealed association of differential methylation patterns with prognostic subgroups based on the IGHV mutation status [14?6], CD38 levels [17], ZAP-70 levels [16], immunogenetic subsets [18], and 17p-deletion status [19]. Earlier, DNA hypermethylation was thought to affect the expression of a gene negatively but the emerging research has suggested that the function and effect of DNA methylation is contextual, and the relationship between DNA methylation and transcription is more complex [20]. In CLL, although association of differential methylation patterns with specific prognostic subgroups in earlier reports highlights the potential of altered gene methylation as a tool to predict clinical outcome, further research is required to establish the relationship between the epigenome and the transcriptome. The present study was carried out to correla.