Silence of the myeloma clones: GPRC5D epigenetic regulation

In this issue of Blood, Ma et al 1 report on the loss of G protein-coupled receptor, class C, group 5, member D (GPRC5D) expression post-anti-GPRC5D chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma (MM), and unravel a potentially reversible silencing mechanism driven by hypermethylation of its regulatory genomic loci.