Innovative evaluation of selinexor and JQ1 synergy in leukemia therapy via C-MYC inhibition.

ABSTRACT:

Background

Acute myeloid leukemia (AML) remains a therapeutic challenge due to drug resistance and relapse. Selinexor, an XPO1 inhibitor, shows limited efficacy as monotherapy, necessitating combination strategies. JQ1, a BET inhibitor targeting MYC, may synergize with Selinexor to enhance antileukemic effects.

Methods

AML cell lines, primary patient samples, and xenograft models (MLL-AF9, CDX, PDX) were treated with Selinexor and JQ1 alone or combined. Synergy was assessed via viability assays (Compusyn/SynergyFinder), apoptosis (flow cytometry/Western blot), and C-MYC suppression (qPCR/CRISPR). In vivo efficacy was evaluated by tumor burden (flow cytometry) and survival.

Results

The combination demonstrated strong synergy (CI < 1, HSA > 10) across AML models, with >

SUBMITTER: Wang PH 

PROVIDER: S-EPMC12063270 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature