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

Table 13

PI3K-Akt signaling.

Gene names	Related pathway	Findings in CLL	Ref.
TCL1A	PI3K-Akt signaling AP1 pathway NF-kB ATM	TCL1A promoter was reported to be hypomethylated in CLL cells and correlated with significant TCL1A transcription enhancement	[139]
PHLPP1	PIP3 signaling PI3K-Akt signaling	Low PHLPP1 expression is reported parallel with its mRNA levels; further analysis detected that the end region of exon 1 may be important in the regulation of PHLPP1 expression although low methylation was observed in the promoter region; compared with normal B cells, the CLL cells with absent or low PHLPP1 expression displayed significantly higher CpG methylation levels and more methylated CpG sites compared than normal B cells and PHLPP1-expressing CLL cells; methylation inhibition led to moderate regulation of PHLPP1 expression	[140]

CLL: chronic lymphocytic leukemia, Ref.: reference, TCL1A: T-cell leukemia/lymphoma 1 oncogene, PHLPP1: PH domain and leucine rich repeat protein phosphatase 1, PI3K-Akt: phosphatidylinositol-3 kinase—protein kinase B, AP1: activator protein 1, NF-kB: nuclear factor kappa-beta, ATM: ataxia-telangectasia mutated, PIP3: phosphatidylinositol (3,4,5)-trisphosphate.