Abstract 180: Expanding the definition of core binding factor leukemia

Abstract

Abstract The core binding factor (CBF) transcription factor complex regulates coding and non-coding genes that play a critical role in hematopoiesis. Chromosomal rearrangements involving the two CFB subunits, RUNX1 and CFB beta, are common in acute myeloid leukemia (AML). The fusion proteins resulting from these rearrangements deregulate the transcription of RUNX1-target genes, including microRNAs critical for KIT-mediated proliferation (e.g. miR-221) and myeloid differentiation (e.g. miR-223). We found that overexpression of miR-17, which downregulates RUNX1 level by targeting RUNX1-UTR, recapitulates the biological effects of CBF-AML fusion proteins by affecting the transcription of common coding and non-coding RUNX1-targets. Consistently, increased levels of miR-17 can be detected in AML patient samples displaying increased KIT level, but without evidence of CBF mutations. Based on these finding, we propose that the definition of CBF-AML leukemia can be expanded to accommodate leukemia induced not only by genetic factors but also epigenetic factors, such as microRNAs targeting RUNX1. Acknowledgements: Funding for this study was provided by a Roswell Park Alliance Foundation award, the University of Rochester-RPCI pilot grant, and the Mark Diamond Research Fund. Citation Format: John A. Fischer, Stefano Rossetti, Arani Datta, Alessandro Beghini, Nicoletta Sacchi. Expanding the definition of core binding factor leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 180. doi:10.1158/1538-7445.AM2015-180