Targeted engagement of β-catenin-Ikaros complexes in refractory B-cell malignancies.

Unlabelled: In most cell types, nuclear β-catenin functions as prominent oncogenic driver and pairs with TCF7-family factors for transcriptional of MYC. Surprisingly, B-lymphoid malignancies not only lacked expression and activating lesions of β-catenin but critically depended on GSK3β for effective β-catenin degradation. Our interactome studies in B-lymphoid tumors revealed that β-catenin formed repressive complexes with lymphoid-specific Ikaros factors at the expense of TCF7.