A Novel Short Latency, High Penetrance Model of KRASMutation-Driven T-Cell Acute Lymphoblastic Leukemia

Introduction: RAS-activating mutations are common in both childhood B- and T-acute lymphoblastic leukemia (ALL). Prior studies of B- and T-ALL have shown that RASmutations become enriched during treatment in minimum residual disease-positive cases, are associated with a poor glucocorticoid response, and are associated with inferior survival in relapsed disease. There is a need for more tractable preclinical models of RASmutation-driven B- and T-ALL. Currently, most genetically-engineered mouse models generated to study KRASG12D-driven ALL have a high latency, low penetrance, and/or necessitate the use of multiple technical manipulations, which can yield inconsistent results. Here, we set out to generate a more efficient and penetrant mouse model of KRASG12D-driven B-ALL or T-ALL.