Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1

Proceedings of the National Academy of Sciences of the United States of America
Joseph D DekkerHaley O Tucker

Abstract

High expression of the forkhead box P1 (FOXP1) transcription factor distinguishes the aggressive activated B cell (ABC) diffuse large B-cell lymphoma (DLBCL) subtype from the better prognosis germinal center B-cell (GCB)-DLBCL subtype and is highly correlated with poor outcomes. A genetic or functional role for FOXP1 in lymphomagenesis, however, remains unknown. Here, we report that sustained FOXP1 expression is vital for ABC-DLBCL cell-line survival. Genome-wide analyses revealed direct and indirect FOXP1 transcriptional enforcement of ABC-DLBCL hallmarks, including the classical NF-κB and MYD88 (myeloid differentiation primary response gene 88) pathways. FOXP1 promoted gene expression underlying transition of the GCB cell to the plasmablast--the transient B-cell stage targeted in ABC-DLBCL transformation--by antagonizing pathways distinctive of GCB-DLBCL, including that of the GCB "master regulator," BCL6 (B-cell lymphoma 6). Cell-line derived FOXP1 target genes that were highly correlated with FOXP1 expression in primary DLBCL accurately segregated the corresponding clinical subtypes of a large cohort of primary DLBCL isolates and identified conserved pathways associated with ABC-DLBCL pathology.

References

Sep 25, 2001·Immunity·A L ShafferL M Staudt
Jun 21, 2002·The New England Journal of Medicine·Andreas RosenwaldUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ildikó GyöryKenneth L Wright
May 27, 2003·Apoptosis : an International Journal on Programmed Cell Death·S P Persengiev, M R Green
Dec 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhiping LiB Hilda Ye
Apr 26, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Xavier SagaertChristiane De Wolf-Peeters
Jul 5, 2006·Nature Immunology·Hui HuAnjana Rao
Mar 8, 2008·Science·Georg LenzLouis M Staudt
Sep 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Georg LenzLouis M Staudt
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
May 22, 2009·Nucleic Acids Research·Timothy L BaileyWilliam S Noble
May 4, 2010·Nature Biotechnology·Cory Y McLeanGill Bejerano
Dec 24, 2010·Nature·Vu N NgoLouis M Staudt
Jul 29, 2011·Nature·Ryan D MorinMarco A Marra
Jan 10, 2012·Annual Review of Immunology·Arthur L ShafferLouis M Staudt
Apr 19, 2012·PloS One·Michael J KlukScott J Rodig
Aug 2, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hye Suk YoonJeremy M Boss
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Apr 13, 2013·Blood·Ainara SagardoyJose A Martinez-Climent
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Gregory C IppolitoHaley O Tucker
Oct 8, 2014·The Journal of Experimental Medicine·Sebastian CarottaStephen L Nutt

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Citations

Sep 30, 2016·Leukemia & Lymphoma·Duncan M Gascoyne, Alison H Banham
Mar 7, 2018·Proceedings of the National Academy of Sciences of the United States of America·Thomas PatzeltJürgen Ruland
Feb 28, 2017·The Journal of Clinical Investigation·Hanjun LiXizhi Guo
Feb 27, 2020·Cell Chemical Biology·ZhiJun QiuRicardo C T Aguiar

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