Interestingly, although DNA2 expression levels were significantly higher in patients with 1q21 gain/amplification, DNA2 activity inhibition significantly depleted both 1q21 and non-1q21 amplified PCs from patients that were refractory to PI-based therapy, possibly because other mechanisms independent of 1q21 (i.e., metabolic rewiring) account for disease progression at the time of MM relapse after PI-based therapy. This evidence concerns the gene DNA2 and Miyoshi myopathy.