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. 2025 May 5;6(3):233-253.
doi: 10.1158/2643-3230.BCD-24-0126.

Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma

Ashwin R Iyer #  1 , Aishwarya Gurumurthy #  1 , Shih-Chun A Chu  1 , Rohan Kodgule  1 , Athalee R Aguilar  1 , Travis Saari  1 , Abdullah Ramzan  1 , Jan Rosa  1 , Juhi Gupta  1 , Arvind Emmanuel  1 , Cody N Hall  1 , John S Runge  1 , Anna B Owczarczyk  1 , Jang W Cho  1 , Matthew B Weiss  1 , Rockwell Anyoha  2 , Kristin Sikkink  3 , Savanna Gemus  3 , Charles P Fulco  2 , Anamarija M Perry  1 , Anthony D Schmitt  3 , Jesse M Engreitz  4   5   6 , Noah A Brown  1 , Marcin P Cieslik  1 , Russell J H Ryan  1
Affiliations

Selective Enhancer Dependencies in MYC-Intact and MYC-Rearranged Germinal Center B-cell Diffuse Large B-cell Lymphoma

Ashwin R Iyer et al. Blood Cancer Discov. .

Abstract

Aberrant MYC activity defines the most aggressive GCB-DLBCLs. We characterized a mechanism of MYC transcriptional activation via a native enhancer that is active in MYC-intact GCB-DLBCL, establishing fitness-sustaining cis- and trans-regulatory circuitry in GCB-DLBCL models that lack MYC enhancer-hijacking rearrangement. See related commentary by Mulet-Lazaro and Delwel, p. 149.

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Conflict of interest statement

K. Sikkink reports personal fees from Arima Genomics outside the submitted work. C.P. Fulco reports a patent for “CRISPR methods and enhancer mapping” (US20200143907A1) pending and is employed by and may hold stock in Sanofi. A.D. Schmitt reports other support from University of Michigan during the conduct of the study and other support from Arima Genomics outside the submitted work; in addition, A.D. Schmitt has a patent for WO2020106776A2 pending and issued. J.M. Engreitz reports grants from the NIH during the conduct of the study and nonfinancial support from 10x Genomics, personal fees from GSK plc, and personal fees from Roche Genentech outside the submitted work; in addition, J.M. Engreitz has a patent for U.S. Patent App. 16/337,846 issued, licensed, and with royalties paid from related to CRISPR technologies used in this work. R.J.H. Ryan reports grants from the NIH/NCI, V Foundation for Cancer Research, and American Society of Hematology and nonfinancial support from Arima Genomics and BioNano Genomics during the conduct of the study, as well as grants from the Hyundai Hope On Wheels Foundation outside the submitted work. No disclosures were reported by the other authors.

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