The MYC dependence of DNMT3B resulting in synthetic lethality upon DNMT3B targeting is of great importance, as triple-relapsed/refractory and extramedullary tumors were recently shown to upregulate G2/M checkpoint gene sets and E2F and MYC targets along with reduced expression of tumor antigens (CD38, SLAMF7, GPRC5D,...) compared to newly diagnosed MM or relapsed MM pre-Dara exposure [58, 59]. Here, GPRC5D is linked to Miyoshi myopathy.