| | Gene name | Related pathway | Findings in CLL | Ref. |
| | WNT5A | Regulation of activated PAK-2, signaling by WNT developmental pathways during embryogenesis | Its expression differs in CLL patients with worse prognosis in the IGHV-mutated subgroup; methylation levels of all the CpG sites in the WNT5A promoter were lowest in the group of the intermediate genome; methylation profile in the memory-like and intermediate genome methylation profile groups were undetectable; WNT5A expression through its promoter methylation correlated with longer treatment-free survival | [95] | | WISP3 | Signaling by WNT | Gene promoter was preferentially methylated in IGVH-mutated CLL | [14, 96] | | LEF1 | Regulation of activated PAK-2 signaling by WNT GSK3 signaling | Methylated promoter status correlated with good prognostic features | [14, 97] | | PAX9 | WNT/Hedgehog/NOTCH signaling | Higher mRNA expression was detected in IGVH-unmutated cases; high expression correlated with higher risk of treatment initiation, shorter time to first treatment, and was predictive of inferior overall survival | [98] | | WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4, and SFRP5 | Inhibitors of the WNT pathway | Over a half of CLL cases showed aberrant gene body methylation of at least one gene | [99–101] | | E-cad | Loss of function contributes to cancer proliferation, invasion, and/or metastasis, signaling by WNT, and regulation of CDH11 | Relative to normal B cells, E-cad was minimally or even absently expressed in globally hypermethylated samples; E-cad hypermethylation was always associated with a simultaneous presence of at least one SFRP gene body hypermethylation | [32, 102, 103] | | PTCH1 | Endochondral ossification signaling by Hedgehog | PTCH1 promoter was reported to be methylated in 46% of the CLL samples examined compared to no case in samples from healthy individuals | [104] |
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CLL: chronic lymphocytic leukemia, Ref.: reference, WNT: wingless-related integration site, WNT5A: WNT family member 5A, WISP3: WNT inducible signaling pathway protein 3, LEF1: lymphoid enhancer-binding factor 1, PAX9: paired box gene 9, WIF1: WNT inhibitory factor 1, DKK3: Dickkopf WNT signaling pathway inhibitor 3, APC: adenomatous polyposis coli gene, SFRP1–5: secreted frizzled-related proteins 1–5, E-cad: cadherin-1, PTCH1: protein patched homolog 1, PAK-2: p21 activated kinase, GSK3: glycogen synthase kinase-3, CDH11: cadherin 11, IGVH: immunoglobulin variable heavy chain gene.
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