The Open Leukemia Journal

2010, 3 : 16-23
Published online 2010 January 22. DOI: 10.2174/1876816401003010016
Publisher ID: TOLEUKEMIAJ-3-16

RESEARCH ARTICLE
 Expression of the FOXP1 Transcription Factor is Post-Transcriptionally Silenced in Normal and Malignant CD138+ Plasma Cells

Philip J. Brown1 , Andrew J. Campbell1 , Linden Lyne1 , Jianxiang Chi1 , Charles H. Lawrie1 , Rajko Kusec2 and Alison H. Banham1, *
1 Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
2 Dubrava University Hospital Zagreb, Croatia and University of Zagreb, Zagreb, Croatia

* Address correspondence to this author at the Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Level 4 Academic Block, John Radcliffe Hospital, Headington, Oxfordshire, OX3 9DU, UK; Tel: +44 (0)1865 220246; Fax: +44 (0)1865 228980; E-mail: alison.banham@ndcls.ox.ac.uk

ABSTRACT

The FOXP1 transcription factor is heterogeneously expressed in normal B cells and is highly expressed in poor prognosis B-cell lymphoma patients. Double immunohistochemical labelling studies identified the striking absence of FOXP1 protein expression in VS38c+, CD38+ and CD138+ plasma cells; prompting an investigation of FOXP1 mRNA and protein expression in multiple myeloma (MM) and the pre-neoplastic plasma cell proliferation monoclonal gammopathy of undetermined significance (MGUS). FOXP1 mRNA expression was assessed by quantitative RT-PCR in normal CD138+ bone marrow plasma cells, MM cell lines (n=4) and cases of MM, including aspirates of whole BM (n=11) and purified CD138+ cells (n=12). Surprisingly both normal and abnormal CD138+ plasma cells expressed the FOXP1 transcript, some cases of each exhibiting high levels, comparable to those in activated B-cell-like diffuse large B-cell lymphoma. However normal CD138+ bone marrow plasma cells, MM cell lines and CD138+ plasma cells in primary MGUS (n=13) and MM biopsies (n=68) were largely devoid of FOXP1 protein expression. The notable exception was two MM patients in which >30% of the CD138+ population was FOXP1+. Mechanisms which block mRNA translation or de-stabilise the FOXP1 protein may silence its expression in plasma cells.

Keywords:

FOXP1, plasma cell, multiple myeloma, post-transcriptional silencing.