Targeting β-catenin nuclear export and protein degradation in high-risk acute lymphoblastic leukemia (ASH 2025) - Nov 4, 2025 - Abstract #abs25-14396; 3371; Pres time: Dec 7, 2025; 06:00 PM - 08:00 PM; Location: OCCC - West Halls B3-B4; "The combination of Selinexorwith GSK3B inhibition (LY2090314) or PSMB8/PSMB9 inhibition (Zetomipzomib/ONX0914) resulted insynergistic nuclear β-catenin accumulation in reporter cells...The identification of β-catenin as an XPO1 cargo protein and thenucleus as a shelter from protein degradation provide a mechanistic rationale for combining XPO1inhibition (selinexor, eltanexor) with GSK3B or immunoproteasome inhibition, which will support thedesign of forthcoming in vivo studies, including xenograft-based preclinical efficacy models in patient-derived B- and T-ALL xenografts. These findings identify β-catenin as a previously unrecognized and functionally significantcargo protein of XPO1 in B- and T-ALL... These findings identify β-catenin as a previously unrecognized and functionally significantcargo protein of XPO1 in B- and T-ALL. Our finding supports a promising combinatorial strategy for thetreatment of r/r ALL by co-targeting nuclear export and β-catenin..."
IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • PSMB8 • PSMB9 • XPO1
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Jodi Forward1,2; Kadriye Nehir Cosgun1; Esma Fera1; Deepa Bhojwani3; David Teachey4; Markus Müschen1
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