title: CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation.
abstract: BACKGROUND
  CD7 is a negative prognostic marker in myeloid malignancies. In acute myeloid leukemia (AML), an inverse correlation exists between expression of wild-type CEBPA and CD7. Aim of this study was to find out whether C/EBPalpha is a negative regulator of CD7 and which other regulatory mechanisms might be involved.
  
  
  RESULTS
  As already described for primary AML cells, the majority of AML cell lines tested were either C/EBPalpha+/CD7- or C/EBPalpha-/CD7+. However, the existence of isolated CD7+ cell lines expressing wild-type C/EBPalpha challenges the notion that C/EBPalpha acts as a unique repressor of CD7. Furthermore, ectopic expression of CEBPA did not reduce CD7 in CD7+ cells and knock-down of C/EBPalpha failed to induce CD7 in CD7- cells. In contrast, the DNA demethylating agent Aza-2'deoxycytidine triggered CD7 expression in CD7- AML and in T-cell lines suggesting epigenetic regulation of CD7. Bisulfite sequencing data confirmed that CpGs in the CD7 exon1 region are methylated in CD7- cell lines, and unmethylated in CD7+ cell lines.
  
  
  CONCLUSIONS
  We confirmed an inverse correlation between the expression of wild-type CEBPA and of CD7 in AML cells. Our results contradict the hypothesis that C/EBPalpha acts as repressor for CD7, and instead show that epigenetic mechanisms are responsible for CD7 regulation, in AML cells as well as in T-cells, the typical CD7 expressing cell type.
authors.affiliation: DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Röhrs
authors.forename: Michaela
authors.initials: M
authors.lastname: Scherr
authors.forename: Julia
authors.initials: J
authors.lastname: Romani
authors.forename: Margarete
authors.initials: M
authors.lastname: Zaborski
authors.forename: Hans G
authors.initials: HG
authors.lastname: Drexler
authors.forename: Hilmar
authors.initials: H
authors.lastname: Quentmeier
mesh_terms: D019011:Antigens, CD7 / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D019011:Antigens, CD7; D022763:CCAAT-Enhancer-Binding Protein-alpha
references.citation: Mol Cell Biol. 2001 Jun;21(11):3789-806
references.pmid: 11340171
references.citation: Curr Opin Hematol. 2006 Jan;13(1):7-14
references.pmid: 16319681
references.citation: Clin Cancer Res. 2005 Feb 15;11(4):1372-9
references.pmid: 15746035
references.citation: Nucleic Acids Res. 1998 Jun 15;26(12):3034-43
references.pmid: 9611252
references.citation: Mol Cell Biol. 1998 Jul;18(7):4301-14
references.pmid: 9632814
references.citation: Leuk Res. 2009 Feb;33(2):326-31
references.pmid: 18718658
references.citation: Mol Cancer. 2010 Feb 22;9:41
references.pmid: 20175919
references.citation: J Hematol Oncol. 2009 Jan 23;2:3
references.pmid: 19166587
references.citation: Nat Genet. 2001 Mar;27(3):263-70
references.pmid: 11242107
references.citation: J Mol Biol. 1987 Jul 20;196(2):261-82
references.pmid: 3656447
references.citation: Blood. 2007 Nov 15;110(10):3706-14
references.pmid: 17671232
references.citation: Leuk Res. 2004 Jan;28(1):43-8
references.pmid: 14630079
references.citation: Cell Cycle. 2003 May-Jun;2(3):251-7
references.pmid: 12734435
references.citation: Nat Genet. 2007 Apr;39(4):457-66
references.pmid: 17334365
references.citation: Mol Cell Biol. 1996 Sep;16(9):4717-25
references.pmid: 8756629
references.citation: Bioinformatics. 2005 Nov 1;21(21):4067-8
references.pmid: 16141249
references.citation: Blood. 1996 Aug 15;88(4):1234-47
references.pmid: 8695841