Using a CRISPR based screen to identify genes dysregulated in AML by T-cells

Abstract Acute Myeloid Leukemia (AML) is the most common hematological malignancy in adults and has a 35% survival rate at 5 years. Genetic heterogeneity makes it highly lethal disease patients develop resistance to therapy. Our lab previously shown that AML, percentage of T-cells bone marrow time diagnosis correlation with overall survival, we have there dysregulation suggesting their involvement immune evasion. However, mechanism by which T-cell activity contributes leukemia not well described. Currently, CRISPR screens are widely used identify sensitivity genes involved killing cancer cells. Based on this strategy, three AML human cell lines (MOLM 14, OCI-AML2 HL-60) several effector target ratios different treatment conditions found majority cells were killed higher ratio. Additionally, stimulating using bispecific antibody conjoins targets improved killing, particularly MOLM 14 line. All these achieved differential T-cells, depending mutational background, evasion gene networks challenge mechanisms. Therefore, our future goal use CRISPR/CAS9 lentiviral library genome-wide screen tumor followed AML. The results experiments will help us better understand mechanisms thus providing roadmap for based therapies combined checkpoint blockade. Supported grant- NIH 1R01CA262145-01A1