A high-throughput drug sensitivity screen identifies novel therapeutic targets in T-PLL. A comprehensive multistep drug screen featuring more than 2500 unique compounds identifies profound T-PLL–specific vulnerability to compounds targeting autophagy (bafilomycin A1), nuclear export (selinexor), and IAP proteins (birinapant). Targeting these novel pathway dependencies has the potential to improve T-PLL patients’ outcomes. IAP, inhibitor of apoptosis; T-PLL, T-cell prolymphocytic leukemia.

A high-throughput drug sensitivity screen identifies novel therapeutic targets in T-PLL. A comprehensive multistep drug screen featuring more than 2500 unique compounds identifies profound T-PLL–specific vulnerability to compounds targeting autophagy (bafilomycin A1), nuclear export (selinexor), and IAP proteins (birinapant). Targeting these novel pathway dependencies has the potential to improve T-PLL patients’ outcomes. IAP, inhibitor of apoptosis; T-PLL, T-cell prolymphocytic leukemia.

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