Contribution of trained immune responses to BCP-ALL development. Children genetically predisposed to BCP-ALL harbor clonally expanded preleukemic cells at birth. A hematopoietic stressor, such as infection, has the potential to trigger ALL at a later time point (2-6 years). The genetically determined immune responses, cytokine release, and basal cytokine levels, especially of interferons, may influence the outgrowth of the leukemic clone. However, the role of earlier-trained innate cells in the control of the preleukemic clone is largely unappreciated thus far. Epidemiological and experimental data suggest that innate immunity can be trained by BCG vaccination or β-glucan application, which substantially reduces the risk of developing BCP-ALL.