Preclinical models of microenvironment resistance also suggest that anti-CD20 monoclonal antibodies and BCR pathway inhibitors may deprive CLL cells of these pro-survival signals[65-67], and may explain the higher rates of response and uMRD remission achieved by venetoclax–rituximab and venetoclax-ibrutinib combination regimens compared to historical results with venetoclax monotherapy[22,44,68,69]. This evidence concerns the gene BCR and B-cell chronic lymphocytic leukemia.