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

Table 3

Gene transcription.

Gene names	Related pathway	Findings in CLL	Ref.
CTLA4	Gene expression (transcription) CD28 costimulation	CTLA4 was hypomethylated in the first exon region and body region and had 128-fold higher expression compared to healthy controls	[37, 59]
LMO2	Angiogenesis and erythropoiesis gene expression (transcription), Assembly of the pre-replicative complex	LMO2 gene body methylated status was identified in IGVH-mutated samples	[26, 60–62]
RARb2	Angiogenesis and erythropoiesis gene expression (transcription), Assembly of the prereplicative complex	Hypermethylation of RARbCpG islands was identified in 29.7% of the analyzed samples in a group of patients while in another series, it was found in 3.1% of the samples studied	[32, 51, 63]
CAT	Gene expression (transcription) innate immune system oxidative stress	A distal CpG island in the promoter region remained methylated both in normal B cells and CLL cells, while variable methylation levels were recorded in the proximal CpG island only in CLL cells exposure of CLL cells to a demethylating agent led to increased catalase mRNA levels	[64]
ZNF540	Gene expression (transcription) MAPK pathway	Methylated status of its gene body was reported in IGVH-unmutated cases	[26, 65]

CLL: chronic lymphocytic leukemia, Ref.: reference, ZNF540: human zinc finger protein 540, LMO2: LIM-only protein 2, RARb2: retinoic acid receptor B2, CAT: catalase, CTLA4: cytotoxic T-lymphocyte associated protein 4, MAPK: mitogen-activated protein kinase, IGVH: immunoglobulin variable heavy chain gene.