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

Table 20

Various other genes investigated in CLL.

Gene names	Related pathway	Findings in CLL	Ref.
LPL	Statin inhibition of cholesterol production; familial hyperlipidemia type 1 pathways	Prognostic marker in CLL gene promoter methylation was associated with IGVH-mutated cases and longer time to treatment	[14, 163, 164]
ABI3	Possible interaction with p21activated kinase inhibits ectopic metastasis of tumor cells	Gene promoter and gene body were frequently methylated in IGVH-unmutated CLL	[14, 26, 165]
CRY1	Melatonin metabolism	Higher mRNA expression was detected in the IGVH-unmutated subgroup; treatment initiation was significantly more frequent among patients with high expression of CRY1; high expression was significantly associated with shorter intervals to first treatment	[98, 153, 154]
SCGB2A1	Androgen receptor signaling pathway	Methylated gene body status was reported in IGVH-unmutated cases	[26, 166]
GATA5	Cooperative activation of the intestinal lactase-phlorizin hydrolase promoter response to elevated platelet cytosolic Ca^2+	GATA 5 promoter hypermethylation was detected in 35.1% of the cases	[51, 167]
DNTT	MYC transcriptional repression DNA-PK pathway	Methylated DNTT gene body was described in IGVH-mutated samples	[26, 168, 169]
SHANK1	Protein-protein interactions at synapses; transmission across chemical synapses	A specific CpG region of the SHANK1 body (hg19) was reported to be hypermethylated when compared to control sample methylation in the same. CpG was detectable in blood samples collected years before CLL diagnosis	[170]
SYN2	Neurotransmitter release cycle; transmission across chemical synapses	SYN2 expression was demonstrated to be reduced in patients with hypermethylated promoter regions and hypomethylated body regions	[37, 171]

CLL: chronic lymphocytic leukemia, Ref.: reference, LPL: lipoprotein lipase, ABI3: Abelson interactor family member 3, CRY1: cryptochrome 1, SCGB2A1: secretoglobin family 2A member 1, GATA5: GATA-binding protein 5, DNTT: DNA nucleotidylexotransferase, SHANK1: SH3 and multiple ankyrin repeat domain 1, SYN2: synapsin II, MYC: MYC proto-oncogene, DNA-PK: DNA-dependent protein kinase, IGVH: immunoglobulin variable heavy chain gene.