BCL6--regulated by AhR/ARNT and wild-type MEF2B--drives expression of germinal center markers MYBL1 and LMO2

Haematologica
Jie DingH Quentmeier

Abstract

Genetic heterogeneity is widespread in tumors, but poorly documented in cell lines. According to immunoglobulin hypermutation analysis, the diffuse large B-cell lymphoma cell line U-2932 comprises two subpopulations faithfully representing original tumor subclones. We set out to identify molecular causes underlying subclone-specific expression affecting 221 genes including surface markers and the germinal center oncogenes BCL6 and MYC. Genomic copy number variations explained 58/221 genes differentially expressed in the two U-2932 clones. Subclone-specific expression of the aryl-hydrocarbon receptor (AhR) and the resulting activity of the AhR/ARNT complex underlaid differential regulation of 11 genes including MEF2B. Knock-down and inhibitor experiments confirmed that AhR/ARNT regulates MEF2B, a key transcription factor for BCL6. AhR, MEF2B and BCL6 levels correlated not only in the U-2932 subclones but in the majority of 23 cell lines tested, indicting overexpression of AhR as a novel mechanism behind BCL6 diffuse large B-cell lymphoma. Enforced modulation of BCL6 affected 48/221 signature genes. Although BCL6 is known as a transcriptional repressor, 28 genes were up-regulated, including LMO2 and MYBL1 which, like BCL6, signif...Continue Reading

Citations

Jan 23, 2016·Current Opinion in Immunology·Lynn M Corcoran, David M Tarlinton
Jun 1, 2016·Frontiers in Cell and Developmental Biology·Sonia Mulero-Navarro, Pedro M Fernandez-Salguero
Dec 3, 2016·PloS One·Hilmar QuentmeierRose-Marie Amini
May 21, 2019·Oncotarget·Kiran MadugulaPooja Jain
Aug 28, 2016·Oncotarget·Hilmar QuentmeierHans G Drexler
Nov 18, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Siraj M El JamalMohamed Hassan
May 8, 2021·Frontiers in Oncology·Nathalie FaumontJean Feuillard

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.