Carcinogenesis is generally regarded as a multi-stepprocess requiring an undefined number of mutations and/or epigenetic changes thatconfer specific growth advantages and/or permit bypass of tumor-suppressivemechanisms [29].Using primary cell lines we demonstrate here that NPM-ALK triggers a durableproliferative arrest via activation of the p53 and Rb pathways withmany features characteristic of senescence. The gene discussed is RB1; the disease is neoplasm.