@article{d54430e005d540ca82fdbcb5271b0dfa,
title = "Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1",
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.",
keywords = "DLBCL, FOXP1, Lymphoma",
author = "Dekker, {Joseph D.} and Daechan Park and Shaffer, {Arthur L.} and Holger Kohlhammer and Wei Deng and Lee, {Bum Kyu} and Ippolito, {Gregory C.} and George Georgiou and Iyer, {Vishwanath R.} and Staudt, {Louis M.} and Tucker, {Haley O.}",
note = "Funding Information: We thank Chhaya Das and Maya Ghosh for help with ChIP and cell culture. Anti-FOXP1 rabbit polyclonal antisera were kindly provided by Dr. Edward Morrissey. Library preparation and Illumina ChIPseq were performed at the NGS core of the MD Anderson Cancer Center. Access to the datasets from the Genotypes and Phenotypes database (dbGaP) (accession no. phs000235) was essential for this study. The dbGaP data were generated by the Cancer Genome Characterization Initiative (CGCI). The Texas Advanced Computing Center (TACC) at The University of Texas at Austin was vital for providing computing resources that have contributed to this manuscript{\textquoteright}s results (https://www.tacc.utexas.edu/). Support for this work was provided by the Intramural Research Program of the National Institutes of Health (NIH) National Cancer Institute, Center for Cancer Research (L.M.S., A.L.S., and H.K.); Lymphoma Research Foundation Fellowship 300463 (to J.D.D.); NIH Grant R01CA31534; Cancer Prevention Research Institute of Texas (CPRIT) Grants RP120348 and RP120459; and the Marie Betzner Morrow Centennial Endowment (H.O.T.). This work was also supported in part by NIH Grants R01CA130075 and R01CA95548 and CPRIT Grants RP120194 (to V.R.I.) and RP100612 (to G.G.).",
year = "2016",
month = feb,
day = "2",
doi = "10.1073/pnas.1524677113",
language = "English (US)",
volume = "113",
pages = "E577--E586",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "5",
}