On these findings, we postulated that MM cells, in order to survive to ongoing endogenous (oxidative and replicative stress) or drug mediated (e.g., bortezomib) DNA damage, switch DNA repair machinery to LIG3-driven-DNA repair, which is able at the same time, to repair nuclear and mtDNA and to allow the acquisition of new genetic changes, leading to disease progression and drug resistance (Fig. 7). The gene discussed is LIG3; the disease is Miyoshi myopathy.