Given that previous studies in cell lines, mouse xenografts and patient-derived tumor samples demonstrated that a shift from glycolysis to high mitochondrial energy metabolism is sufficient to promote PI resistance25, and that higher levels of DNA2 expression were associated with worse progression-free survival after PI-based therapy (Supplementary Fig. 3G), we evaluated whether DNA2 activity inhibition was synthetically lethal in plasma cells (PCs) isolated from patients whose disease failed PI-based therapy. The gene discussed is DNA2; the disease is neoplasm.