In this study, we found that one of the mechanisms through which c-Myc inhibition reduced cell survival of both MM and PEL cell lines was the interruption of the cross-talk that c-Myc establishes with the IRE1α/XBP1 axis, which was accompanied by the upregulation of CHOP, the downregulation of RAD51 and BRCA1 and the increase of DNA damage. Here, DDIT3 is linked to Miyoshi myopathy.