Transcriptional activity of a T-ALL PDX line following in vitro treatment with idasanutlin, navitoclax (ABT-263), or combination therapy

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with an umet need for improved therapies. We explored the potentially synergic combination of MDM2 inhibition and Bcl-2, Bcl-xL inhibition through cotreatment of T-ALL models with idasanutlin and navitoclax. In order to understand the early transcriptional changes induced by this combination therapy, we performed RNA sequencing on drug treated cells. Overall design: T-ALL PDX line was cultured with cytokine support and treated for 16 hours. Confirmation of cell viability was performed via Annexin V flow cytometric assay (>80% not yet apoptotic). Cells were treated with DMSO, 300nM navitoclax, 1.5uM idasanutlin, or combination therapy.