American Association for Cancer Research
Browse

Supplementary Table S1 from BCL6 Antagonizes NOTCH2 to Maintain Survival of Human Follicular Lymphoma Cells

Download (195 kB)
dataset
posted on 2023-04-03, 21:23 authored by Ester Valls, Camille Lobry, Huimin Geng, Ling Wang, Mariano Cardenas, Martín Rivas, Leandro Cerchietti, Philmo Oh, Shao Ning Yang, Erin Oswald, Camille W. Graham, Yanwen Jiang, Katerina Hatzi, Xabier Agirre, Eric Perkey, Zhuoning Li, Wayne Tam, Kamala Bhatt, John P. Leonard, Patrick A. Zweidler-McKay, Ivan Maillard, Olivier Elemento, Weimin Ci, Iannis Aifantis, Ari Melnick

Supplementary Table S1. BCL6 target genes on FL patient samples ChIp-onChIP.

Funding

Lymphoma Research Foundation

Chemotherapy Foundation

Seventh Framework Programme

NIH

Leukemia and Lymphoma Society

National Basic Research Programme

National Natural Science Foundation of China

Chinese Academy of Sciences

History

ARTICLE ABSTRACT

Although the BCL6 transcriptional repressor is frequently expressed in human follicular lymphomas (FL), its biological role in this disease remains unknown. Herein, we comprehensively identify the set of gene promoters directly targeted by BCL6 in primary human FLs. We noted that BCL6 binds and represses NOTCH2 and NOTCH pathway genes. Moreover, BCL6 and NOTCH2 pathway gene expression is inversely correlated in FL. Notably, BCL6 upregulation is associated with repression of NOTCH2 and its target genes in primary human and murine germinal center (GC) cells. Repression of NOTCH2 is an essential function of BCL6 in FL and GC B cells because inducible expression of Notch2 abrogated GC formation in mice and killed FL cells. Indeed, BCL6-targeting compounds or gene silencing leads to the induction of NOTCH2 activity and compromises survival of FL cells, whereas NOTCH2 depletion or pathway antagonists rescue FL cells from such effects. Moreover, BCL6 inhibitors induced NOTCH2 expression and suppressed growth of human FL xenografts in vivo and primary human FL specimens ex vivo. These studies suggest that established FLs are thus dependent on BCL6 through its suppression of NOTCH2.Significance: We show that human FLs are dependent on BCL6, and primary human FLs can be killed using specific BCL6 inhibitors. Integrative genomics and functional studies of BCL6 in primary FL cells point toward a novel mechanism whereby BCL6 repression of NOTCH2 drives the survival and growth of FL cells as well as GC B cells, which are the FL cell of origin. Cancer Discov; 7(5); 506–21. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 443