| | Gene name | Related pathway | Findings in CLL | Ref. |
| | ZAP70 | NFAT, TCR signaling, Rho GTPases signaling, NF-kB, Erk signaling | Negative prognostic marker in CLL methylation of a CpG site downstream of transcriptional start site correlated with IGVH-mutated and favorable prognosis | [114–118] | | ANGPT2 | MIF-mediated glucocorticoid regulation, TGF-β pathway, Erk, PI3K-Akt signaling | Higher methylation levels of gene promoter in the IGVH-mutated cases, lower degree of methylation associated with particularly poor prognosis, methylation of its promoter leads to gene silencing | [14, 119–121] | | ROR1 | GPCR signaling, Erk, signaling by WNT | ROR1 expression was upregulated; hypomethylation in the promoter as well as in the body region was demonstrated | [37, 122] | | DAPK1 | Programmed cell death dimerization of procaspase-8, MAPK-Erk | Promoter hypermethylation associated with the downregulation of DAPK1 expression | [123] | | ADAM12 | Cell-to-cell and cell-to-matrix interactions, fertilization, muscle tissue development, and neurogenesis EGFR, MAPK-Erk pathway | 48% of the samples were partially methylated and 52% were reported to be unmethylated compared to 20% and 80.6%, respectively, in healthy individuals, an association statistically significant | [124] | | AIRE | Regulated by the MAPK pathway | Methylated gene body was observed in IGVH-mutated cells | [26, 125] | | RASGRP3 | RAF/MAPK cascade regulation of activated PAK-2 | Methylated gene body correlated with the IGVH-mutated status | [26, 126–128] | | PPP1R3A | Beta-adrenergic signaling | Methylated gene body was observed in IGVH-mutated cases | [26, 129] |
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CLL: chronic lymphocytic leukemia, Ref.: reference, ZAP70: zeta chain of T-cell receptor-associated protein kinase 70, ANGPT2: angiopoietin 2, ROR1: receptor tyrosine kinase-like orphan receptor 1, DAPK1: death-associated protein kinase 1, ADAM12: disintegrin and metalloproteinase domain-containing protein 12, AIRE: autoimmune regulator, RASGRP3: rat sarcoma guanyl releasing protein 3, PPP1R3A: protein phosphatase 1 regulatory subunit 3A, NFAT: nuclear factor of activated T cells, TCR: T-cell receptor, NF-kB: nuclear factor kappa-beta, MAPK: mitogen-activated protein kinase, Erk: extracellular signal-regulated kinase, MIF: macrophage migration inhibitory factor, TGF-β: transforming growth factor beta, PI3K-Akt: phosphatidylinositol-3-kinase—protein kinase B, GPCR: G protein-coupled receptor, WNT: wingless-related integration site, RAF: rapidly accelerated fibrosarcoma, EGFR: epidermal growth factor receptor, PAK-2: p21 activated kinase 2, IGVH: immunoglobulin variable heavy chain gene.
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