We also identified signaling modulations in myeloma B lymphopoiesis from hscs to switched memory B cells to PBs or PCs; significantly elevated levels of MMSET, MYD88, c-Myc, CD243, Notch-1, and CD47 were noted even in premalignant conditions, with variable IRF-4 levels within MM stages and B cell subsets. Here, NSD2 is linked to plasma cell myeloma.