Prevention of childhood Acute Lymphoblastic Leukemia immunology links oncology

ongoing

PreventALL analyzes genetic risk in infection induced ALL and will pioneer leukemia prevention. Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer and it remains a major cause of death in children aged 2-6 years in high-income countries. Exposure to infection, as a potential trigger for the development of childhood ALL was theorized a century ago with several possibilities of exposure to infection in infancy. Consequently, the overall objectives of PreventALL is to systematically analyze postnatally the genetic risk to develop B-cell-precursor (BCP)-ALL and to decipher the infectious mechanism by which exposure to infection causes BCP-ALL. This opens a new horizon for the understanding of leukemia etiology and foster innovation in the development of novel preventive strategies such as diet supplementation or vaccination. To this end, appropriate methods of postnatal risk calculation and in vivo models are needed. We have recently developed the first in vivo murine models with infection-dependent BCP-ALL, based on a genetic predisposition. PreventALL aims to extend this knowledge and to set off for cutting edge research to explore the synergy of genetic predisposition and exposure to infection in BCP-ALL as a proof-of-concept for the role of infection in precancerous disease. In PreventALL Aim 1 will compile novel strategies to identify patients at risk for BCP-ALL, in Aim 2 I will develop preclinical infection-dependent BCP-ALL in vivo models and identify the mechanism how infection triggers BCP-ALL with respect to the genetic predisposition and finally Aim 3 will set up to develop preclinical prevention programs. In summary, PreventALL will establish a significant milestone in the understanding of childhood leukemia and set the starting point for the development of novel and innovative leukemia precision prevention.