NPM-ALK regulates a dynamic equilibrium to inactivate the p53 tumor suppressor pathway. NPM-ALK activates the JNK SAP kinase and PI 3-kinase/Akt pathways as previously reported.^6,24  These pathways act to sequester and inactivate p53 via direct binding to JNK or MDM2 leading to degradation via the proteosome. JNK also targets MDM2 for degradation. PI 3-kinase activity leads to tethering of p53 protein to cytoskeletal structures in the cytoplasm, where it is primed for nuclear entry (represented by a curved dashed arrow).