Targeting immunoproteasome-dependent β-catenin degradation as a therapeutic strategy in Relapsed/Refractory acute lymphoblastic leukemia (ASH 2025) - Nov 4, 2025 - Abstract #abs25-14244; 5092; Pres time: Dec 8, 2025; 06:00 PM - 08:00 PM; Location: OCCC - West Halls B3-B4; "Interestingly, treatment with M3258 (a selective PSMB8 inhibitor) did not interfere with β-cateninprotein degradation, suggesting that combined inhibition of both PSMB8 and PSMB9 is required forefficient inhibition...Likewise, genetic deletion of LEF1 rescued cellviability and caused resistance to Zetomipzomib and ONX-0914, highlighting the importance ofrepressive LEF1/β-catenin complexes in B- and T-ALL cells to suppress MYC. Our findings uncovered a previously unrecognized dependency of B- and T-ALL cells onimmunoproteasome-mediated β-catenin degradation to sustain MYC expression and survival... Our findings uncovered a previously unrecognized dependency of B- and T-ALL cells onimmunoproteasome-mediated β-catenin degradation to sustain MYC expression and survival. Targetingthe immunoproteasome, rather than the generic proteasome, offers a more selective strategy forlymphoid malignancies, with the potential for reduced off-target toxicity compared to..."
Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Solid Tumor • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • T-cell Acute Lymphoblastic Lymphoma • CTNNB1 • MYC • PSMB10 • PSMB5 • PSMB8 • PSMB9 • TCF7
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Jodi Forward1,2; Kadriye Nehir Cosgun1; Tianhao Yin1; Esma Fera1; Deepa Bhojwani3; David Teachey4; Markus Müschen1
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