We observed that in NPM-ALK signaling pathway-driven mesenchymal large cell lymphomas, over-activation of NPM-ALK would lead to a significant increase in phosphorylation of the DNA damage response mediated by the MAPK-ERK 1/2 pathway, resulting in the accumulation of DNA damage and γH2AX microfoci in the nucleus of the cells at the DNA double-strand breaks (DSBs), and ultimately due to the oncogenic stress response inducing impaired lymphoma growth and apoptosis [136, 137]. This evidence concerns the gene ALK and lymphoma.