Table 1. Key genes inflicted with aberrant DNA methylation in CLL.
| Gene/pathway | Functional role | References |
|---|---|---|
|
CLL prognostic genes | ||
|
ZAP70 |
Involved in B cell/T cell signaling. Methylation related with decreased expression and IGHV-mutated CLL. |
23
,
42
|
|
LPL |
Known CLL prognosticator. Methylation associated with decreased expression and IGHV-mutated CLL. |
42
,
81
|
|
CLLU1 |
Prognostic marker in CLL. Methylation correlates with decreased expression and IGHV-mutated CLL. |
42
,
83
|
|
NOTCH1 |
Mutations of NOTCH1 are associated progressive CLL disease and are a marker of poor prognosis. |
42
,
84
|
|
Tumor suppressors | ||
|
WISP3 |
Involved in WNT signaling. Implicated in breast cancer. Preferentially methylated in IGHV-mutated CLL. |
42
,
85
|
|
VHL |
Associated with von Hippel-Lindau syndrome, a hereditary cancer syndrome predisposing to cancer. Differentially methylated between IGHV-mutated and unmutated CLL. Preferentially methylated in IGHV-unmutated CLL |
44
,
86
|
|
ABI3 |
ABI3 protein inhibits metastasis and tumor migration. ABI3 was found to be differentially methylated between IGHV-mutated and unmutated CLL. Frequently methylated in IGHV-unmutated CLL |
42
,
44
,
87
|
|
DAPK1 |
Positive mediator of apoptosis. Potential tumor suppressor. Commonly methylated in CLL, indicated in familial CLL. |
31
|
|
Survival/proliferation related genes | ||
|
MYB |
Proto-oncogene regulates miRNA155 in CLL. Methylated in IGHV-mutated CLL |
42
,
88
|
|
LEF1 |
Involved in WNT signaling. Pro-survival factor in CLL, methylated in good-prognostic CLL. |
42
,
89
|
|
SNRP2 and SNRP4 |
WNT signaling inhibitors commonly methylated in CLL. |
20
|
|
Transcription factor genes | ||
|
TWIST2 |
Known silencer of p53 in hematological malignancies. Hypermethylation common in IGHV-mutated CLL. |
22
|
|
HOXA4 |
Transcription factor important for cell development. Commonly methylated in poor-prognostic CLL. |
26
|
|
miRNAs* | ||
|
miR-34a, miR-129, miR-708,miR-124–1, miR-203, miR-9 |
Regulatory sequences thought to regulate gene expression of key genes involved in CLL pathogenesis such as p53, XPO1 and NOTCH1 |
49
-
51
,
58
|
|
Epigenetic regulator genes |
|
|
| HDAC4/HDAC9 | Histone deacetylases, differentitally methylated between prognostic CLL subgroups. | 42 , 90 |
*
Anticipated targets of the bold marked miRNAs are correspondingly highlighted in bold.