This study investigates the synergistic potential of Selinexor, a selective XPO1 inhibitor, and JQ1, a BET bromodomain inhibitor, in targeting acute myeloid leukemia (AML). AML remains a therapeutic challenge because of drug resistance and relapse after initial treatment.  Although Selinexor has demonstrated limited efficacy as monotherapy in AML, its combination with JQ1 was hypothesized to enhance therapeutic outcomes via dual inhibition of C-MYC expression. 

To evaluate this combination strategy, researchers used a comprehensive panel of  human AML cell lines, patient-derived AML samples, and in vivo models— including MLL-AF9 bone marrow transplantation, MOLM13-derived xenografts, and patient-derived xenografts (PDX).The CellTiter-Glo® 2.0 Cell Viability Assay (Promega) was used to assess cell viability after treatment with Selinexor, JQ1 or the two drugs in combination. <

The combination therapy significantly reduced cell viability, enhanced apoptosis (as confirmed by PARP cleavage and Annexin V/PI assays), and inhibited cell cycle progression, particularly reducing S-phase proliferation. The combination outperformed single-agent treatments across all models tested. 

In vivo results reinforced the in vitro findings: the combination therapy reduced the leukemic burden across tissues and extended survival in both CDX and PDX modes. These findings suggest that co-targeting nuclear export and epigenetic regulation of oncogenic drivers like C-MYC may represent a compelling strategy for overcoming AML resistance. <

Keywords:acute myeloid leukemia, Selinexor, JQ1, XPO1 inhibitor, BET inhibitor, C-MYC, apoptosis, BRD4, cell viability assay, patient-derived xenograft, CellTiter-Glo 2.0, combination therapy, drug synergy. <

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