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...

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Veröffentlicht in:Blood 2008-03, Vol.111 (5), p.2816-2824
Hauptverfasser: Brown, Philip J., Ashe, Sally L., Leich, Ellen, Burek, Christof, Barrans, Sharon, Fenton, James A., Jack, Andrew S., Pulford, Karen, Rosenwald, Andreas, Banham, Alison H.
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Sprache:eng
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Zusammenfassung: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-09-115113