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Background  In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients.    Results  The integration of DNA methylation profile ( n  = 14) with the gene expression profile ( n  = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals. The mRNA expression levels of 17 genes identified to be differentially methylated and/or differentially expressed was further examined in early stage CLL patients ( n  = 93) by quantitative real time PCR (RQ-PCR). Significant differences were observed in the mRNA expression of  MEIS1 ,  PMEPA1 ,  SOX7 ,  SPRY1 ,  CDK6 ,  TBX2 , and  SPRY2  genes in CLL cells as compared to B-cells from healthy individuals. The analysis in the  IGHV  mutation based categories (Unmutated = 39, Mutated = 54) revealed significantly higher mRNA expression of  CRY1  and  PAX9  genes in the  IGHV  unmutated subgroup ( p  < 0.001). The relative risk of treatment initiation was significantly higher among patients with high expression of  CRY1  (RR = 1.91,  p  = 0.005) or  PAX9  (RR = 1.87,  p  = 0.001). High expression of  CRY1  (HR: 3.53,  p  < 0.001) or  PAX9  (HR: 3.14,  p  < 0.001) gene was significantly associated with shorter time to first treatment. The high expression of  PAX9  gene (HR: 3.29, 95% CI 1.172–9.272,  p  = 0.016) was also predictive of shorter overall survival in CLL.    Conclusions  The DNA methylation changes associated with mRNA expression of  CRY1  and  PAX9  genes allow risk stratification of early stage CLL patients. This comprehensive analysis supports the concept that the epigenetic changes along with the altered expression of genes have the potential to predict clinical outcome in early stage CLL patients.    Electronic supplementary material  The online version of this article (doi:10.1186/s13148-017-0356-0) contains supplementary material, which is available to authorized users.

clinical epigenetics

Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia