Role of GCN2 in guiding the cellular and molecular response to asparaginase in the pancreas

Asparaginase is a chemotherapy agent used in the treatment of acute lymphoblastic leukemia. Asparaginase can cause severe pancreatitis but the molecular basis is unknown. In liver of mice, the eIF2 kinase GCN2 is essential for mitigating metabolic stress caused by asparaginase. This study examined the role of GCN2 in the pancreas of mice treated with asparaginase. Eight week old wild type or GCN2 KO mice were injected once daily for 8 d with either 3 IU/g BW of saline or asparaginase. Eight hours after final injection, mice were sacrificed and pancreata were weighed and harvested. In GCN2 KO mice treated with asparaginase, pancreas weights were significantly increased (P