Initiating genetic lesions are primarily ETV6-RUNX1 or hyperdiploidy, probably occurring as developmental accidents. They arise in utero possibly in foetal liver early B lineage lymphopoiesis . Secondary mutations are primarily RAG-mediated copy number alterations. ~1% figure: ALL is initiated in utero at a rate that exceeds by 100-fold, the incidence of disease indicating a low penetrance and a critical role for factors promoting chronic inflammation and the secondary mutations. Adapted from . See text for references.