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

Title
Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1
Authors
박대찬Joseph D DekkerArthur L ShafferHolger KohlhammerWei DengBum-Kyu LeeGregory C IppolitoGeorge GeorgiouVishwanath R IyerLouis M StaudtHaley O Tucker
Issue Date
2016-02
Publisher
Proceedings of the National Academy of Sciences of the United States of America
Citation
VOL 113, NO 5-E586
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-kappa B 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.
URI
http://pubs.kist.re.kr/handle/201004/67099
ISSN
0027-8424
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