Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report

gene, which encodes for trypsinogen, and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. In conclusion, this study finds a shared genetic predisposition between asparagi-nase-associated pancreatitis and non-asparaginase-associated pancreatitis, and targeting the trypsinogen activation pathway may enable identification of effective interventions for asparaginase-associ-ated pancreatitis. increased calcium (Ca ++ ) efflux from the endoplasmic reticulum. This in turn leads to opening of Ca ++ release activated (CRAC) channels, further increasing intracellular calcium levels, reducing ATP levels and allowing activation of inactive trypsinogen to active trypsin.