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

Bohne, Arend; Schlee, Cornelia; Mossner, Max; Thibaut, Julia; Heesch, Sandra; Thiel, Eckhard; Hofmann, Wolf-Karsten; Baldus, Claudia D.

doi:10.1016/j.leukres.2008.11.012

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Volume 33, Issue 6 , Pages 817-822, June 2009

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

Charité, University Hospital Berlin, Campus Benjamin Franklin, Department of Hematology and Oncology, Hindenburgdamm 30, 12203 Berlin, Germany

Received 26 June 2008; received in revised form 12 November 2008; accepted 13 November 2008. published online 07 March 2011.

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 (ERG3Δex12) 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.