Identification of Genetic Pathways Controlling Resistance to Standard Combination Chemotherapy in Acute Myeloid Leukemia

Abstract

Abstract Introduction: Resistance to chemotherapy, manifesting as refractory or relapsed disease, remains the largest cause of mortality in acute myeloid leukemia (AML). Clonal evolution through the acquisition of new mutations, or selection of resistant clones, appears responsible in many cases of relapsed disease. We used a genome-wide CRISPR-Cas9 loss of function screen to identify deleted genes, which mediate resistance to Cytarabine (AraC) and anthracycline, Doxorubicin (Dox) in AML. Methods: Dose response was defined using MTS viability assays, with synergism determined using the Chou-Talalay method. For the screen, Cas9-expressing OCI-AML3 cells were tran..