Targeted inhibitors of Bruton tyrosine kinase (BTKi) and the anti-apoptotic protein B-cell lymphoma 2 (BCL2i—the most advanced example in development being venetoclax [Ven]) are highly effective first-line strategies for treatment of CLL with significant activity demonstrated across all genomic risk subgroups. Here, IBTK is linked to B-cell chronic lymphocytic leukemia.