Abstract
BACKGROUND: Exportin-1 (XPO1), a key regulator of nucleocytoplasmic transport, is frequently dysregulated in acute myeloid leukemia (AML) and contributes to leukemogenesis, disease progression and therapeutic resistance. Selective inhibitors of nuclear export (SINEs), especially selinexor and eltanexor, have shown promising antileukemic potential. However, their clinical value, optimal therapeutic positioning and rational use in AML remain to be fully clarified. METHODS: We collected and reviewed relevant literature to summarize the biological roles of XPO1 in AML and the therapeutic potential of XPO1 inhibitors in preclinical and clinical settings. RESULTS: In this review, we focus on the nuclear export function of XPO1 and its pathogenic role in AML. We summarize the mechanisms of action, preclinical evidence, clinical trial results, adverse effects, resistance mechanisms and potential response biomarkers associated with XPO1 inhibitors in AML. CONCLUSIONS: XPO1 inhibition has emerged as a promising therapeutic strategy for AML, offering a novel approach to targeting aberrant nucleocytoplasmic transport and overcoming treatment resistance. Future studies should focus on optimizing dosing schedules, identifying predictive biomarkers and developing effective combination strategies in molecularly selected AML populations. KEY POINTS: XPO1 hyperactivation rewires nucleocytoplasmic transport and sustains leukaemogenic programs in genetically defined acute myeloid leukaemia (AML) subsets. Selective XPO1 inhibitors (selinexor, eltanexor) show preferential activity in NPM1-mutated, DEK::NUP214-positive and SF3B1-mutated myeloid neoplasms. Combination strategies with hypomethylating agents, BCL-2 inhibitors and other targeted therapies enhance depth and durability of responses but are limited by toxicity. Future clinical trials should focus on molecularly selected populations, biomarker-guided dosing and translational endpoints such as measurable residual disease (MRD) and clonal dynamics.