Kapoor and colleagues report that CLL chronically resistant to ibrutinib (a Bruton tyrosine kinase (BTK) inhibitor) are sensitized to venetoclax partly also by a STAT3-mediated Bcl-2 upregulation in resistant CLL, implying a shift in the type of Bcl-2 family protein dependence [39]. Here, BTK is linked to B-cell chronic lymphocytic leukemia.