Epigenetic control of differential expression of specific ERG isoforms in acute T-lymphoblastic leukemia.
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 (ERG3Deltaex12) 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.
Bohne
Arend
A
Department of Hematology and Oncology, Charité, University Hospital Berlin, Berlin, Germany.
Schlee
Cornelia
C
Mossner
Max
M
Thibaut
Julia
J
Heesch
Sandra
S
Thiel
Eckhard
E
Hofmann
Wolf-Karsten
WK
Baldus
Claudia D
CD
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005091:Exons; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
D017931:DNA Primers; C072312:ERG protein, human; D015513:Oncogene Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D000077209:Decitabine; D001374:Azacitidine