We therefore hypothesized that, in keeping with our prior suggestion that NPM–ALK may replace the TCRβ signalling cascade16, NPM–ALK may allow an immature hematopoietic cell to bypass thymic β-selection to a stage when TCRα VJ rearrangement becomes possible, thus enabling abnormal T lymphoid differentiation and implying a thymic origin to at least a proportion of ALCL. This evidence concerns the gene NPM1 and anaplastic large cell lymphoma.