ERG Transcriptional Networks in Primary Acute Leukemia Cells Implicate a Role for ERG in Deregulated Kinase Signaling

作者：Bock Juliane; Mochmann Liliana H; Schlee Cornelia; Farhadi Sartangi Nasrin; Goellner Stefanie; Mueller Tidow Carsten; Baldus Claudia D^*

来源：PLos One, 2013, 8(1): e52872.

DOI：10.1371/journal.pone.0052872

High expression of the E26 transforming sequence related gene ( ERG) is associated with poor prognosis in a subgroup of leukemia patients with acute myeloid (AML) and acute T-lymphoblastic leukemia (T-ALL). In a previous study we proposed that ERG overexpression may deregulate several signaling cascades in acute leukemia. Herein, we further expand those studies by identifying a consensus of biological targets in primary blasts of newly diagnosed acute leukemia patients. Our findings of chromatin immunoprecipitation-on-chip of primary samples revealed 48 significantly enriched single genes including DAAM1 and NUMB. Significantly enriched signaling pathways included WNT/beta-catenin, p53, and PI3K/AKT with ERG overexpression inducing dephosphorylation of AKT(Ser473) relative to non ERG expressing K562 cells. Cell based ERG overexpression studies also revealed drug resistance to multi-kinase inhibitor, BAY 43-9006 (Sorafenib) and to the tyrosine kinase inhibitor TKI258. Thus in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors.

• 出版日期2013-1-3