DT2216 as a single agent significantly reduced cell viability in iPSC-HPCs with JAK2^V617F mutation and JAK2-mut AML cell lines. (A) BCL2L1 mRNA expression in iPSC-HPCs with or without JAK2^V617F mutation from a patient with MPN. ∗∗∗∗P < .0001. (B) Cell viability of iPSC-HPCs with the indicated concentrations of DT2216 for 72 hours. (C) Western blots for iPSC-HPCs with or without JAK2^V617F mutation treated with 1 μM DT2216 for 72 hours. β-Actin was used as the loading control for the western blot. (D) BH3 profiling of iPSC-HPCs with or without JAK2^V617F mutation. The BH3 peptides and drugs were categorized by their target molecules. (E) IC₅₀ values of venetoclax at 24 hours in AML cell lines. ∗∗∗P < .001. (F) Cell viability of JAK2-mut parental (Pa) and Ruxo-Re AML cell lines (HEL, SET2, and UKE-1) with the indicated concentrations of DT2216 for 72 hours. (G) BH3 profiling of JAK2-mut AML cell lines and the MOLM13 AML cell line (BCL-2 dependent). (H) BH3 profiling of paired SET2 and HEL Pa and Ruxo-Re cell lines and the MOLM3 cell line.