Abstract
High level MYC expression is associated with almost all human cancers. JQ1, a chemical compound that inhibits MYC expression is therapeutically effective in preclinical animal models in midline carcinoma, and Burkitt’s lymphoma (BL). Here we show that JQ1 does not inhibit MYC expression to a similar extent in all tumor cells. The BL cells showed a ∼90% decrease in MYC transcription upon treatment with JQ1, however, no corresponding reduction was seen in several non-BL cells. Molecularly, these differences appear due to requirements of Brd4, the most active version of the Positive Transcription Elongation Factor B (P-TEFb) within the Super Elongation Complex (SEC), and transcription factors such as Gdown1, and MED26 and also other unknown cell specific factors. Our study demonstrates that the regulation of high levels of MYC expression in different cancer cells is driven by unique regulatory mechanisms and that such exclusive regulatory signatures in each cancer cells could be employed for targeted therapeutics.
Highlights
Lymphomas are broadly classified into two categories: Hodgkin’s and non-Hodgkin’s lymphoma (NHL) [1]
Both HeLa and BAL17 cells continued this resistance at concentrations up to 5 mM, while MYC RNA in Burkitt’s lymphoma (BL) cells was uniformly decreased by,90% when treated with 1 mM of JQ1 for a period of two hours (Fig. 1A)
Recent advances in this area include the discovery of a small molecule inhibitor, JQ1 that decreases MYC expression and is therapeutically effective in pre-clinical animal models of midline carcinoma and in BL cells
Summary
Lymphomas are broadly classified into two categories: Hodgkin’s and non-Hodgkin’s lymphoma (NHL) [1]. The two most common forms of aggressive NHL are diffuse large B cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) [1,2,3]. Translocation of the proto-oncogene MYC into one of the immunoglobulin gene loci [IG-MYC translocation; mostly of the t(8;14)q24;q32 type] resulting in aberrant MYC expression is regarded as the dominant genetic event in the genesis of BL and about 10% of DLBCL [4]. MYC can undergo oncogenic deregulation via high-level gene amplification as well as mutations in cis-regulatory elements in several cancer types (e.g., myeloma, colon carcinoma and neuroblastoma) [5,6]. Though high expression is restricted to BLs, MYC target expression varies on a lower level across non-BL and intermediate lymphomas and constitutes a negative prognostic marker in these lymphomas
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
