Although natural selection among cells could represent a powerful mechanism of tissue surveillance, the effects of lack of cell competition on development or disease remain unclear. In Nature, Rodewald and colleagues show that removing competition in the thymus by deleting the supply of bone marrow–derived progenitor cells leads to emergence of T cell acute lymphoblastic leukemia. 'Fit' competitors, such as wild-type or Rag1−/− progenitor cells, suppress the emergence of leukemia if restoration occurs within 1 week of the establishment of thymic autonomy, whereas 'unfit' competitors, such as Il7ra−/− or Il2rg−/− progenitor cells, do not. Deprivation of progenitor cells induces delays in the physiological replacement of the thymocyte compartment at CD4−CD8− double-negatve stages 2 and 3 and induces the emergence of leukemia with the genomic lesions, gene-expression profiles and Notch1-activating mutations characteristic of T cell acute lymphoblastic leukemia. In addition, the data indicate that the availability of interleukin 7 (IL-7) might represent an important aspect of cell competition in the thymus.

Nature 509, 465–470 (2014)