Today, double Hit (DH) or Double Expresser (DE) DLBCL comprises ∼20–25% of newly diagnosed high-grade (HG) DLBCL, is defined by either the translocation or overexpression of MYC and Bcl-2 (less frequently, Bcl-6), and is correlated with R-CHOP treatment resistance with a 2-year overall survival of ∼20% [37,38,39]. This evidence concerns the gene DDIT3 and diffuse large B-cell lymphoma.