title: Epigenetic regulation of WNT signaling in chronic lymphocytic leukemia.
abstract: Certain WNT and WNT network target genes are expressed at higher or lower levels in chronic lymphocytic leukemia compared with normal B-cells. This includes upregulation of nuclear complex genes, as well as genes for cytoplasmic proteins and WNT ligands and their cognate receptors. In addition, epigenetic silencing of several negative regulators of the WNT pathway have been identified. The balance between epigenetic downregulation of negative effector genes and increased expression of positive effector genes demonstrate that the epigenetic downregulation of WNT antagonists is one mechanism, perhaps the main mechanism, that is permissive to active WNT signaling in chronic lymphocytic leukemia. Moreover, constitutive activation of the WNT network and target genes is likely to impact on additional interacting signaling pathways. Based on published studies, we propose a model of WNT signaling that involves mainly permissive expression, and sometimes overexpression, of positive effectors and downregulation of negative regulators in the network. In this model, DNA methylation, histone modifications and altered expression of microRNA molecules interact to allow continuous WNT signaling.
authors.forename: Lynda B
authors.initials: LB
authors.lastname: Bennett
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Arthur
authors.forename: Farahnaz B
authors.initials: FB
authors.lastname: Rahmatpanah
authors.forename: Sam I
authors.initials: SI
authors.lastname: Hooshmand
authors.forename: Charles W
authors.initials: CW
authors.lastname: Caldwell
references.citation: Leukemia. 2009 Jun;23(6):1159-63
references.pmid: 19158830
references.citation: Nature. 2000 Jul 6;406(6791):86-90
references.pmid: 10894547
references.citation: Trends Biochem Sci. 2008 Dec;33(12):592-600
references.pmid: 18926707
references.citation: Haematologica. 2010 Jan;95(1):110-8
references.pmid: 19713228
references.citation: Mol Cell Biol. 2007 Dec;27(23):8164-77
references.pmid: 17923689
references.citation: Blood. 2006 Nov 1;108(9):3143-51
references.pmid: 16840734
references.citation: Bioessays. 2008 Nov;30(11-12):1110-25
references.pmid: 18937364
references.citation: Carcinogenesis. 2007 Jan;28(1):60-70
references.pmid: 16774933
references.citation: Cell Signal. 2009 Nov;21(11):1541-7
references.pmid: 19298854
references.citation: Cancer Res. 2005 Dec 15;65(24):11241-6
references.pmid: 16357125
references.citation: Mol Cell. 2008 May 23;30(4):507-18
references.pmid: 18498752
references.citation: Leukemia. 2009 Jun;23(6):1019-28
references.pmid: 19194470
references.citation: Leukemia. 2006 Oct;20(10):1855-62
references.pmid: 16900213
references.citation: Blood. 2009 Apr 16;113(16):3744-53
references.pmid: 19096009
references.citation: Curr Drug Targets. 2009 Jul;10(7):620-31
references.pmid: 19601766
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15417-22
references.pmid: 18824696
references.citation: Leuk Lymphoma. 2005 Sep;46(9):1275-85
references.pmid: 16109604
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Apr 12;363(1495):1333-47
references.pmid: 18192173
references.citation: Leukemia. 2007 May;21(5):965-72
references.pmid: 17344921
references.citation: Hepatology. 2009 Aug;50(2):472-80
references.pmid: 19585654
references.citation: Nat Rev Mol Cell Biol. 2009 Apr;10(4):276-86
references.pmid: 19305417
references.citation: Nat Struct Mol Biol. 2009 Mar;16(3):304-311
references.pmid: 19234465
references.citation: RNA. 2009 Aug;15(8):1443-61
references.pmid: 19561119
references.citation: Science. 2001 Aug 10;293(5532):1074-80
references.pmid: 11498575
references.citation: PLoS One. 2009 Jul 31;4(7):e6459
references.pmid: 19649288
references.citation: Bioinformatics. 2006 Jul 15;22(14):e431-9
references.pmid: 16873504
references.citation: Blood. 2009 Jan 22;113(4):856-65
references.pmid: 18796623
references.citation: Blood. 2009 Oct 29;114(18):3872-9
references.pmid: 19717645
references.citation: Methods Mol Biol. 2009;563:303-52
references.pmid: 19597793
references.citation: BMC Cancer. 2009 May 21;9:159
references.pmid: 19460168
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D155-8
references.pmid: 18957447
references.citation: Clin Cancer Res. 2008 Jan 15;14(2):396-404
references.pmid: 18223214
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18151-6
references.pmid: 17989227
references.citation: Cancer Lett. 2009 Nov 28;285(2):116-26
references.pmid: 19464788
references.citation: Nature. 2009 Jul 2;460(7251):66-72
references.pmid: 19571879
references.citation: Science. 2007 Oct 19;318(5849):447-50
references.pmid: 17761849
references.citation: Hematol Oncol. 2006 Sep;24(3):134-8
references.pmid: 16841369
references.citation: Cell Signal. 2008 May;20(5):795-802
references.pmid: 18160255
references.citation: Cancer Cell. 2003 Nov;4(5):349-60
references.pmid: 14667502
references.citation: J Biol Chem. 2008 Jun 13;283(24):16818-29
references.pmid: 18408217
references.citation: Blood. 2009 May 28;113(22):5568-74
references.pmid: 19336759
references.citation: Leuk Lymphoma. 2009 Mar;50(3):419-26
references.pmid: 19347729
references.citation: BMC Immunol. 2006 Jun 29;7:13
references.pmid: 16808837
references.citation: Br J Cancer. 2009 Aug 18;101(4):699-706
references.pmid: 19638978
references.citation: Cancer Res. 2008 Nov 1;68(21):8743-51
references.pmid: 18974116
references.citation: Blood. 2007 Jul 15;110(2):735-42
references.pmid: 17463171
references.citation: Genes Dev. 2006 May 1;20(9):1123-36
references.pmid: 16618801
references.citation: Nature. 2007 Aug 2;448(7153):553-60
references.pmid: 17603471
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3118-23
references.pmid: 14973184
references.citation: Cell Signal. 2007 Apr;19(4):659-71
references.pmid: 17188462
references.citation: Leuk Res. 2006 Jan;30(1):29-32
references.pmid: 16054689
references.citation: Nat Genet. 2006 Dec;38(12):1359-60
references.pmid: 17133218
references.citation: Epigenetics. 2009 Jul 1;4(5):307-312
references.pmid: 28001119
references.citation: Endocr Rev. 2005 Dec;26(7):898-915
references.pmid: 16126938
references.citation: Pharmacol Ther. 2009 Sep;123(3):344-52
references.pmid: 19464317
references.citation: Braz J Med Biol Res. 2007 Nov;40(11):1435-40
references.pmid: 17934639
references.citation: J Clin Oncol. 2009 Nov 10;27(32):5459-68
references.pmid: 19826124
references.citation: Ann N Y Acad Sci. 2007 Apr;1100:60-74
references.pmid: 17460165
references.citation: BMC Bioinformatics. 2005 Jan 20;6:12
references.pmid: 15661078
references.citation: Cancer Res. 2006 Jan 15;66(2):653-8
references.pmid: 16423993
references.citation: Eur J Cancer. 2009 May;45(7):1129-1136
references.pmid: 19211243
references.citation: Nat Med. 2007 Aug;13(8):944-51
references.pmid: 17632527
references.citation: Cell Signal. 2008 Jun;20(6):1198-208
references.pmid: 18396013
references.citation: J Cell Biol. 2009 Jun 1;185(5):811-26
references.pmid: 19487454
references.citation: Genes Chromosomes Cancer. 2009 Sep;48(9):828-41
references.pmid: 19530241
references.citation: Blood. 2009 Nov 5;114(19):4179-85
references.pmid: 19745069
references.citation: Leukemia. 2007 May;21(5):949-55
references.pmid: 17361218
references.citation: Leuk Res. 2010 Feb;34(2):221-8
references.pmid: 19682743
references.citation: J Mol Biol. 2009 Aug 28;391(4):691-702
references.pmid: 19576224
references.citation: J Immunol. 2002 Jul 15;169(2):758-69
references.pmid: 12097378
references.citation: J Clin Invest. 2005 Mar;115(3):755-64
references.pmid: 15711642
references.citation: Exp Hematol. 2002 Jan;30(1):26-33
references.pmid: 11823034
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3047-52
references.pmid: 18287027
references.citation: Mol Cell Biol. 2007 Nov;27(22):7802-15
references.pmid: 17875931
references.citation: Int J Mol Med. 2009 Jun;23(6):763-9
references.pmid: 19424602
references.citation: N Engl J Med. 2005 Oct 27;353(17):1793-801
references.pmid: 16251535
references.citation: Cell Signal. 2008 Oct;20(10):1697-704
references.pmid: 18555664
references.citation: Int J Biochem Cell Biol. 2010 Mar;42(3):381-90
references.pmid: 19631281
references.citation: Cell Cycle. 2007 May 2;6(9):1001-5
references.pmid: 17457051
references.citation: Stem Cells. 2004;22(5):849-60
references.pmid: 15342948
references.citation: Dev Dyn. 2010 Jan;239(1):56-68
references.pmid: 19655378
references.citation: Gene. 2002 Apr 17;288(1-2):119-27
references.pmid: 12034501
references.citation: J Biol Chem. 2009 Jan 30;284(5):3323-3333
references.pmid: 19047045
references.citation: Nature. 2006 Feb 16;439(7078):871-4
references.pmid: 16357870
references.citation: Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R93-R100
references.pmid: 15809278
references.citation: Nat Genet. 2007 Feb;39(2):232-6
references.pmid: 17200670
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10
references.pmid: 17890317
references.citation: Cancer Res. 2009 Mar 15;69(6):2623-9
references.pmid: 19258506
references.citation: Leukemia. 2009 Nov;23(11):2118-28
references.pmid: 19657365
references.citation: Carcinogenesis. 2006 Jun;27(6):1121-5
references.pmid: 16699174
references.citation: Stem Cells. 2005 Sep;23(8):1180-91
references.pmid: 15955826
references.citation: Curr Oncol Rep. 2007 Sep;9(5):345-52
references.pmid: 17706162
references.citation: Exp Cell Res. 2009 Oct 15;315(17):2941-52
references.pmid: 19591824
references.citation: Exp Cell Res. 2009 Oct 1;315(16):2690-704
references.pmid: 19563800
references.citation: Eur J Cancer. 2009 May;45(7):1137-1145
references.pmid: 19346125
references.citation: Histol Histopathol. 2009 Mar;24(3):385-98
references.pmid: 19130408
references.citation: J Biol Chem. 2005 Mar 11;280(10):9498-508
references.pmid: 15618220
references.citation: Cell. 2007 May 18;129(4):823-37
references.pmid: 17512414
references.citation: Br J Haematol. 2009 Nov;147(4):471-83
references.pmid: 19751240
references.citation: Blood. 2009 Jul 9;114(2):404-14
references.pmid: 19398721
references.citation: J Clin Oncol. 2008 Sep 20;26(27):4497-503
references.pmid: 18662968
references.citation: Best Pract Res Clin Haematol. 2007 Sep;20(3):385-97
references.pmid: 17707828
references.citation: PLoS One. 2009 Sep 11;4(9):e6986
references.pmid: 19750229
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
references.pmid: 12434020
references.citation: Blood. 1995 May 15;85(10):2870-6
references.pmid: 7742549
references.citation: Blood. 1992 Oct 15;80(8):2074-80
references.pmid: 1382719
references.citation: Leuk Res. 2006 Sep;30(9):1135-9
references.pmid: 16427695
references.citation: Cell Death Differ. 2010 Feb;17(2):215-20
references.pmid: 19498445
references.citation: Curr Med Chem. 2009;16(17):2075-85
references.pmid: 19519382
references.citation: Cancer Res. 2009 Apr 15;69(8):3278-82
references.pmid: 19351815
references.citation: Blood. 2009 Jun 18;113(25):6411-8
references.pmid: 19211935
references.citation: Cell. 2007 Feb 23;128(4):669-81
references.pmid: 17320505
references.citation: Blood. 2009 Oct 15;114(16):3367-75
references.pmid: 19636060
references.citation: J Biol Chem. 2003 Nov 14;278(46):45937-45
references.pmid: 12928438
references.citation: Bioinformatics. 2009 Aug 1;25(15):1991-3
references.pmid: 19435746
references.citation: RNA. 2007 Feb;13(2):223-39
references.pmid: 17185360
references.citation: Nat Chem Biol. 2009 Feb;5(2):100-7
references.pmid: 19125156
references.citation: Nat Med. 2008 Nov;14(11):1271-7
references.pmid: 18931683
references.citation: Annu Rev Med. 2009;60:167-79
references.pmid: 19630570
references.citation: Blood. 2005 Feb 1;105(3):959-67
references.pmid: 15466934
references.citation: Lab Invest. 2009 Jun;89(6):708-16
references.pmid: 19349957
references.citation: J Exp Med. 2001 Dec 3;194(11):1639-47
references.pmid: 11733578
references.citation: Blood. 2007 Jun 1;109(11):4944-51
references.pmid: 17327404
references.citation: J Immunol. 2005 Mar 15;174(6):3749-56
references.pmid: 15749915
references.citation: J Cell Biochem. 2009 Feb 1;106(2):337-43
references.pmid: 19115259
references.citation: Cancer Biol Ther. 2004 Oct;3(10):989-94
references.pmid: 15467427
references.citation: J Pathol. 2008 May;215(1):13-20
references.pmid: 18348159
references.citation: Cancer Biol Ther. 2006 Sep;5(9):1059-64
references.pmid: 16940750
references.citation: Clin Cancer Res. 2009 Jun 15;15(12):3970-7
references.pmid: 19509171
references.citation: Epigenomics. 2009 Oct;1(1):39-61
references.pmid: 20495622
references.citation: Nat Rev Drug Discov. 2006 Dec;5(12):997-1014
references.pmid: 17139285
references.citation: Cancer Res. 2004 Apr 1;64(7):2424-33
references.pmid: 15059895
references.citation: Int J Oncol. 2009 May;34(5):1411-5
references.pmid: 19360354
references.citation: Mol Cancer Res. 2008 Dec;6(12):1928-36
references.pmid: 19074837
references.citation: J Biol Chem. 2002 Nov 1;277(44):41762-9
references.pmid: 12205098
references.citation: J Clin Pathol. 2008 Nov;61(11):1214-9
references.pmid: 18765431
references.citation: Nat Rev Genet. 2007 Apr;8(4):286-98
references.pmid: 17339880
references.citation: J Clin Oncol. 2009 Aug 10;27(23):3808-14
references.pmid: 19470922
references.citation: Cell. 2005 Jan 28;120(2):169-81
references.pmid: 15680324
references.citation: Leukemia. 2008 Feb;22(2):330-8
references.pmid: 17989717
references.citation: Clin Cancer Res. 2007 Jul 15;13(14):4042-5
references.pmid: 17634527
references.citation: Mol Cell Biol. 2007 Nov;27(21):7560-73
references.pmid: 17785445
references.citation: J Cell Biol. 2008 Mar 24;180(6):1087-100
references.pmid: 18347071
references.citation: J Cell Biol. 2003 Sep 1;162(5):899-908
references.pmid: 12952940
references.citation: Genes Dev. 2004 Jul 1;18(13):1592-605
references.pmid: 15231737
references.citation: Cancer Res. 2008 Jun 1;68(11):4116-22
references.pmid: 18519670
references.citation: Bioorg Med Chem. 2009 Sep 1;17(17):6257-63
references.pmid: 19665384
references.citation: Int J Cancer. 2010 Mar 1;126(5):1109-20
references.pmid: 19653274
references.citation: Blood. 2009 Nov 26;114(23):4832-42
references.pmid: 19789386
references.citation: Int J Biochem Cell Biol. 2009 Jan;41(1):87-95
references.pmid: 18834952
references.citation: J Cell Biochem. 2007 Aug 1;101(5):1109-24
references.pmid: 17546602
references.citation: Cell Res. 2009 Jan;19(1):71-88
references.pmid: 19002158