The Role of Methylation in Chronic Lymphocytic Leukemia and Its Prognostic and Therapeutic Impacts in the Disease: A Systematic Review

Table 4

RNA polymerase I promoter opening.

Gene names	Related pathway	Findings in CLL	Ref.
MAFB	RNA polymerase I promoter opening, nervous system development regulation of hematopoiesis	Differentially methylated regions of the MAFB gene have been associated with survival features in CLL cohorts where the hypermethylated status was linked to inferior post-treatment survival	[66]
HOXA4	RNA polymerase I promoter opening	Hypermethylated promoter region was associated with the IGVH-unmutated status and inferior clinical outcome, strong predictor of time to first treatment, independent of the IGVH mutational and CD38 expression status	[67, 68]
TET1	RNA polymerase I promoter opening, gene expression (transcription)	TET1 gene body was variously methylated, 5-aza 2′-deoxycytidine exposure to CLL cells led to decreased occupancy of EZH2 over the TET1 promoter and conversely to the loss of TET1 expression, increased expression of specific intronic transcripts associated with decreased TET1 promoter activity	[69]

CLL: chronic lymphocytic leukemia, Ref.: reference, MAFB: V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, HOXA4: homeobox A4, TET1: tet methylcytosine dioxygenase 1, CD38: cluster of differentiation 38, EZH2: enhancer of Zeste 2 polycomb repressive complex 2 subunit, IGVH: immunoglobulin variable heavy chain gene.