Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL.
The FOXP1 forkhead transcription factor is targeted by recurrent chromosome translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high-level FOXP1 protein expression has been linked to a poor prognosis. Western blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly identified the atypical high-level expression of 2 smaller, 60 to 65 kDa, FOXP1 isoforms in all 5 of those with the activated B cell (ABC)-like DLBCL subtype and in a subgroup of primary DLBCL. The anti-FOXP1 (JC12) monoclonal antibody cannot distinguish FOXP1 isoforms by immunohistochemistry, a finding that may be clinically relevant as high-level expression of the full-length FOXP1 protein was observed in some germinal center-derived DLBCLs. ABC-like DLBCL-derived cell lines were observed to express 2 novel, alternatively spliced FOXP1 mRNA isoforms, encoding N-terminally truncated proteins. These transcripts and the smaller protein isoforms were induced as a consequence of normal B-cell activation, which thus represents an additional mechanism for up-regulating FOXP1 expression in lymphomas. The expression of potentially oncogenic smaller FOXP1 isoforms may resolve the previously contradictory findings that FOXP1 represents a favorable prognostic marker in breast cancer and an adverse risk factor in B-cell lymphomas.
Brown
Philip J
PJ
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Ashe
Sally L
SL
Leich
Ellen
E
Burek
Christof
C
Barrans
Sharon
S
Fenton
James A
JA
Jack
Andrew S
AS
Pulford
Karen
K
Rosenwald
Andreas
A
Banham
Alison H
AH
D017398:Alternative Splicing / Q000235:genetics; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology*; D001706:Biopsy; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005091:Exons / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D010544:Peroxidases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D020033:Protein Isoforms; D012097:Repressor Proteins; D010544:Peroxidases