CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation.
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.
Röhrs
Sonja
S
DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.
Scherr
Michaela
M
Romani
Julia
J
Zaborski
Margarete
M
Drexler
Hans G
HG
Quentmeier
Hilmar
H
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
D019011:Antigens, CD7; D022763:CCAAT-Enhancer-Binding Protein-alpha
Mol Cell Biol. 2001 Jun;21(11):3789-806
11340171
Curr Opin Hematol. 2006 Jan;13(1):7-14
16319681
Clin Cancer Res. 2005 Feb 15;11(4):1372-9
15746035
Nucleic Acids Res. 1998 Jun 15;26(12):3034-43
9611252
Mol Cell Biol. 1998 Jul;18(7):4301-14
9632814
Leuk Res. 2009 Feb;33(2):326-31
18718658
Mol Cancer. 2010 Feb 22;9:41
20175919
J Hematol Oncol. 2009 Jan 23;2:3
19166587
Nat Genet. 2001 Mar;27(3):263-70
11242107
J Mol Biol. 1987 Jul 20;196(2):261-82
3656447
Blood. 2007 Nov 15;110(10):3706-14
17671232
Leuk Res. 2004 Jan;28(1):43-8
14630079
Cell Cycle. 2003 May-Jun;2(3):251-7
12734435
Nat Genet. 2007 Apr;39(4):457-66
17334365
Mol Cell Biol. 1996 Sep;16(9):4717-25
8756629
Bioinformatics. 2005 Nov 1;21(21):4067-8
16141249
Blood. 1996 Aug 15;88(4):1234-47
8695841