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

Table 14

Rho GTPases/Rhodopsin-like receptors.

Gene names	Related pathway	Findings in CLL	Ref.
ET-1	GPCR signaling, class A/1 (Rhodopsin-like receptors), NF-kB	ET-1 is involved in survival, drug resistance, and growth signaling of leukemic cells; basal expression levels of ET-1 are affected when high methylation levels in a region of ET-1 first intron are detected	[141]
PLD1	Cell survival and protection from apoptosis. Glycerophospholipid biosynthesis signaling by Rho GTPases	Unmethylated PLD1 gene body was reported in IGVH-mutated cases	[26, 142]
DLC1	Signaling by Rho GTPases	In advanced Rai stage CLL cases, aberrant methylation of DLC1 promoter was identified in 89.7% of the samples examined	[36]
S1PR4	Involved in cell migration, GPCR signaling, class A/1 (Rhodopsin-like receptors)	In a study where cells from CLL, Richter’s transformed CLL and normal B cells were analyzed, and S1PR4 displayed significantly higher promoter methylation levels in Richter’s syndrome compared to the other groups	[85]
GHSR	Class A/1 (Rhodopsin-like receptors), GPCR signaling	Remarkable hypermethylation at the promoter region and first exon of the gene was detected; abnormal methylation was able to distinguish with high sensitivity and specificity malignant from normal cells; GHSR hypermethylation was reported to be identified even in early disease stages	[143]

CLL: chronic lymphocytic leukemia, Ref.: reference, PLD1: phospholipase D1, DLC1: deleted in liver cancer 1, S1PR4: sphingosine 1-phosphate receptor 4, ET-1: endothelin 1, GHSR: growth hormone secretagogue receptor type 1, GPCR: G protein-coupled receptor, NF-kB: nuclear factor kappa-beta, IGVH: immunoglobulin variable heavy chain gene.