Epigenetic regulation of reelin expression in multiple myeloma.

Reelin (RELN) is a secreted extracellular matrix glycoprotein associated with the positioning and migration of neuronal cells and a few types of non-neuronal cells. We have previously reported RELN expression in multiple myeloma cells. High RELN expression was associated with poor prognosis and enhanced myeloma cell adhesion and survival. To examine the epigenetic regulation of RELN expression, its promoter methylation status in myeloma-derived cell lines and primary tumour cells from myeloma patients were analysed. RELN expression was moderate in CD19+ B cells and was upregulated in CD138+ plasma cells. A further upregulated RELN transcription was found in multiple myeloma cells. High expressions of RELN in myeloma cell lines as well as in patients were associated with hypomethylation in RELN promoter region. Demethylation increased RELN transcription in vitro. Together, we established that the methylation status of the promoter proximal cytosine-phospho-guanine dinucleotides determines the expression of RELN in myeloma cells. Copyright © 2016 John Wiley & Sons, Ltd.