Expression of the FOXP1 transcription factor is post-transcriptionally silenced in normal and malignant CD138+ plasma cells

Autor: Brown, Philip, Campbell, Andrew, Lyne, Linden, Chi, Jianxiang, Lawrie, Charles, Kušec, Rajko, Banham, Alsion.
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Popis: 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=15). 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. Like PAX5, FOXP1 has an essential role in early B-cell differentiation and is silenced during terminal B-cell differentiation to plasma cells.
Databáze: OpenAIRE