BCL2L1 and B-cell chronic lymphocytic leukemia: Antiapoptotic proteins such as Bcl-2 and Bcl-xL are implicated in resistance to chemotherapeutics including cyclophosphamide, methotrexate, melphalan, and corticosteroids.[44] Notably, the Bcl-2 inhibitor venetoclax, currently approved for chronic lymphocytic leukemia, has demonstrated promising clinical activity in MM.[45,46] Histone deacetylase 6 (HDAC6), which mediates aggresome-dependent protein degradation, has emerged as a therapeutic target for overcoming PI resistance.