When human myeloma MM1S cells were treated with KDOAM-25 at concentrations consistent with inhibition of KDM5B-mediated H3K4me3 demethylation in myeloma cells, anti-proliferative effects were observed with anticipated genome-wide increases in H3K4me3 levels as demonstrated by quantitative ChIP-seq experiments. Here, KDM5B is linked to plasma cell myeloma.