BCL9 plays an essential role as a coactivator in the WNT/β-catenin signaling pathway by mediating the recruitment of pygopus to the nuclear β-catenin-TCF complex.29 BCL9 is frequently overexpressed in a variety of solid tumors including colorectal cancer, multiple myeloma, and HCC.33 We revealed through gain-of-function and loss-of-function studies that BCL9 plays an oncogenic role in HCC: its activation contributes to WNT/β-catenin signaling hyperactivation, an immune-excluded tumor microenvironment, and tumor growth and metastasis. This evidence concerns the gene BCL9 and plasma cell myeloma.