Accession Number:

ADA620612

Title:

Understanding Selective Downregulation of c-Myc Expression through Inhibition of General Transcription Regulators in Multiple Myeloma

Descriptive Note:

Annual rept. 15 Jun 2014-14 Jun 2015

Corporate Author:

DANA-FARBER CANCER INST BOSTON MA

Personal Author(s):

Report Date:

2015-06-01

Pagination or Media Count:

61.0

Abstract:

Through analysis of the chromatin and transcriptional landscape of Multiple Myeloma MM and other tumors, this project has endeavored to provide an explanatory mechanism for how treatment with inhibitors of chromatin regulators can selectively target oncogene transcription, and to understand how chromatin and transcription are altered to promote tumorigenesis. Here we report the discoveries that BET bromodomains are required to communicate enhancer mediated pro-inflammatory signal dependent transduction Brown et al., 2014, that translocations of the IgH enhancer to the MYC locus in MM expose both enhancer driven and MYCE2F driven regulatory programs to BET bromodomain inhibition Fulciniti et al., submitted, and that master transcription factors co-operate with one another and BET bromodomains to establish oncogenic state in MM and other tumors Lin et al., submitted. These efforts have yielded insights into the dynamic transcriptional control of oncogenic cell state, the development of novel and extendable experimental and computational approaches, and therapeutic insights into the consequences of systemic in vivo BET bromodomain inhibition.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE