Cancer: Darwinian tumour suppression.

Abstract

Competition for access to a survival factor has been found to explain why incoming cells from the bone marrow replace resident cells in the thymus. Reducing this competition can cause tumours to form. See Article p.465 In the thymus, T cells develop from precursor cells that are constantly replaced by newly arriving bone marrow progenitor cells. Hans-Reimer Rodewald and colleagues show that this is the result of competition between the 'old' and 'new' cells. In the absence of cell competition, when the influx of new bone marrow progenitor cells is blocked in mice, old cells reacquire the ability to self-renew and eventually become transformed, leading to the development of T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease. At the same time there are changes in gene expression and the appearance of genetic mutations often also found in human T-ALL. Thus cell competition can act as a tumour-suppressor mechanism. This work may also help to explain the widely discussed T-cell leukaemia seen in X-linked severe combined immune deficiency patients after therapy with gene-corrected autologous progenitors.