Epigenetic control of differential expression of specific ERG isoforms in acute T-lymphoblastic leukemia

Abstract Expression of ERG is of prognostic significance in acute myeloid leukemia (AML) and T-lymphoblastic leukemia (T-ALL) pointing to its role in leukemogenesis. To unravel its transcriptional regulation we analyzed the expression of ERG specific isoforms. Expression of the two main isoforms ERG...

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Bibliographic Details
Published in:Leukemia research 2009-06, Vol.33 (6), p.817-822
Main Authors: Bohne, Arend, Schlee, Cornelia, Mossner, Max, Thibaut, Julia, Heesch, Sandra, Thiel, Eckhard, Hofmann, Wolf-Karsten, Baldus, Claudia D
Format: Article
Language:English
Subjects:
Acute leukemia
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Base Sequence
CpG Islands
DNA Methylation
DNA Primers
Epigenesis, Genetic
ERG
Exons
Hematology, Oncology and Palliative Medicine
Hypermethylation
Isoform expression
Oncogene Proteins - genetics
Polymerase Chain Reaction
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Protein Isoforms - genetics
Trans-Activators - genetics
Transcriptional Regulator ERG
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Summary:Abstract Expression of ERG is of prognostic significance in acute myeloid leukemia (AML) and T-lymphoblastic leukemia (T-ALL) pointing to its role in leukemogenesis. To unravel its transcriptional regulation we analyzed the expression of ERG specific isoforms. Expression of the two main isoforms ERG2 and ERG3 was found in AML and normal CD34+ cells, whereas T-ALL blasts only expressed ERG isoforms harboring exon 5 ( ERG3 ) lacking expression of ERG2 . Bisulfite sequencing revealed hypermethylation of a CpG island within the ERG2 promoter region in T-ALL. Treatment of the T-lymphoblastic cell line BE13 with decitabine led to re-expression of ERG2 and pyrosequencing showed concordant DNA hypomethylation, thus confirming a methylation regulated expression of ERG2 . Moreover, the identification of a new ERG isoform ( ERG3 Δ ex12 ) suggests the association with different interaction partners and adds to the complexity of downstream pathways mediated by the expression of specific ERG transcripts in acute leukemia.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2008.11.012