The oligodendrocyte lineage transcription factor 2 (OLIG2) is epigenetically regulated in acute myeloid leukemia

Item Type:	Article
Title:	The oligodendrocyte lineage transcription factor 2 (OLIG2) is epigenetically regulated in acute myeloid leukemia
Creators Name:	Yalcin, A. and Kovarbasic, M. and Wehrle, J. and Claus, R. and Becker, H. and Abdelkarim, M. and Gaidzik, V.I. and Schmidts, A. and Wäsch, R. and Pahl, H.L. and Döhner, K. and Bullinger, L. and Duyster, J. and Lübbert, M. and Hackanson, B.
Abstract:	DNA methylation differences between normal tissue and cancerous tissue resulting in differential expression of genes are a hallmark of acute myeloid leukemia (AML) and can provide malignant cells with a growth advantage via silencing of specific genes, for example, transcription factors. Oligodendrocyte lineage transcription factor 2 (OLIG2) was reported to be differentially methylated and associated with prognosis in AML and, as reported for acute lymphoblastic leukemia and malignant glioma, may play a role in malignant transformation. We report that DNA methylation of OLIG2 is associated with decreased expression of mRNA in AML cell lines and patients. Moreover, in cell lines, decreased mRNA expression also translated into decreased OLIG2 protein expression. Treatment of non-expressing cell lines PL-21 and U-937 with the demethylating agent decitabine resulted in robust re-expression of OLIG2 on mRNA and protein levels. Furthermore, stable overexpression of OLIG2 in non-expressing cell lines Kasumi-1 and U-937, using a lentiviral vector system, led to moderate growth inhibition after 4 days and resulted in signs of differentiation in U-937 cells. Interestingly, although CD34 + cells from healthy donors and 10 of 12 AML patients exhibited no protein expression, OLIG2 was expressed in two patients, both bearing the translocation t(15;17), corresponding to OLIG2 expression in NB-4 cells, also harboring t(15;17). In conclusion, we provide first evidence that OLIG2 is epigenetically regulated via DNA methylation and expressed in a subset of AML patients. OLIG2 may exert antiproliferative activity in leukemia cell lines, and its potential leukemia-suppressing role in AML warrants further investigation.
Keywords:	Acute Disease, Azacitidine, Cell Differentiation, Cell Proliferation, Decitabine, DNA Methylation, Genetic Epigenesis, HL-60 Cells, Jurkat Cells, Leukemic Gene Expression Regulation, Myeloid Leukemia, Oligodendrocyte Transcription Factor 2, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Tumor Cell Line, U937 Cells, Western Blotting
Source:	Experimental Hematology
ISSN:	1873-2399
Publisher:	Elsevier
Volume:	55
Page Range:	76-85
Date:	November 2017
Official Publication:	https://doi.org/10.1016/j.exphem.2017.07.009
PubMed:	View item in PubMed

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