Novel therapies targeting BCR signaling (e.g., ibrutinib and idelalisib) and B-cell leukemia/lymphoma-2 (BCL-2) family proteins (e.g., venetoclax) provide significantly improved outcomes for both previously untreated CLL patients and those with adverse disease (e.g., 17p deletion and/or TP53 mutation or complex karyotype). Here, BCR is linked to B-cell chronic lymphocytic leukemia.