Transcriptional Repression of C/EBPα by Histone Deacetylases in Acute Myeloid Leukemia
In acute myeloid leukemia (AML), fusion proteins such as AMLl-ETO recruit co-repressors and histone deacetylases (HDACs) to their target genes. We compared gene expression in fresh AML blasts with and without HDAC inhibition by Trichostatin A (TSA) to identify genes that are repressed by HDAC dependent mechanisms. After exposure to TSA, C/EBPa expression in leukemic blasts increased up to ten-fold in 31% (5/16) of the analyzed AML samples. For several other transcription factors (C/EBPε, Hox A10, AMLl, PBX1, MLL, HLX), no induction by TSA was found. We also analyzed whether C/EBPα expression was directly regulated by AML associated fusion proteins in inducibly transfected U937 cells. Expression of C/EBPa was significantly repressed by AMLl-ETO and PML-RARα. Interestingly, TSA led to C/EBPa induction in U937 cells expressing PML-RARa, but not in PLZF-RARa or AML1- ETO containing cells. Taken together, these findings provide further evidence for C/EBPα dysregulation in AML.
KeywordsAcute Myeloid Leukemia U937 Cell Normal Bone Marrow Leukemic Blast Acute Myeloid Leukemia Case
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