Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells

P>FOXP2 mutation causes a severe inherited speech and language defect, while the related transcription factors FOXP1, FOXP3 and FOXP4 are implicated in cancer. FOXP2 mRNA and protein expression were characterised in normal human tissues, haematological cell lines and multiple myeloma (MM) patients' samples. FOXP2 mRNA and protein were absent in mononuclear cells from different anatomical sites, lineages and stages of differentiation. However, FOXP2 mRNA and protein was detected in several lymphoma (8/20) and all MM-derived cell lines (n = 4). FOXP2 mRNA was expressed in bone marrow samples from 96% of MM patients (24/25), 66 center dot 7% of patients with the pre-neoplastic plasma cell proliferation monoclonal gammopathy of undetermined significance (MGUS) (6/9), but not in reactive plasma cells. The frequency of FOXP2 protein expression in CD138+ plasma cells was significantly higher in MGUS (P = 0 center dot 0005; mean 46 center dot 4%) and MM patients (P < 0 center dot 0001; mean 57 center dot 3%) than in reactive marrows (mean 2 center dot 5%). FOXP2 (> 10% nuclear positivity) was detectable in 90 center dot 2% of MM (55/61) and 90 center dot 9% of MGUS (10/11) patients, showing more frequent expression than CD56 and labelling 75% of CD56-negative MM (9/12). FOXP2 represents the first transcription factor whose expression consistently differentiates normal and abnormal plasma cells and FOXP2 target genes are implicated in MM pathogenesis.