Darwinian Evolution of Acute Lymphoblastic Leukaemia

Overall survival for paediatric ALL is favourable, but after relapse this rate drops dramatically. Many patients who relapse will have an aggressive drug resistant disease, clonally evolved from a presentation or ancestral clone, acquiring mutations in a Darwinian manner. We previously characterised a presentation/relapse pair derived from a t(17;19) pre B ALL patient sample in which the relapse has a 5q deletion spanning 5 genes, including NR3C1, the glucocorticoid receptor. Competitive transplantation showed the presentation outcompetes the relapse, except under dexamethasone treatment. This lead to the hypoth…