Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation

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:

Keywords

acute myeloid leukaemia / exportin-1 / selective inhibitors of nuclear export / venetoclax-based combinations / XPO1 inhibition

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2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.