Unravelling the suboptimal response of TP53‐mutated chronic lymphocytic leukaemia to ibrutinib.

Summary: TP53‐disrupted chronic lymphocytic leukaemia (CLL) patients show a suboptimal long‐term response to ibrutinib. We hereby report that ibrutinib‐induced in vitro apoptosis and proliferation inhibition were significantly lower in TP53‐mutated (TP53‐M) CLL cells compared to TP53 wild‐type cells. Contrariwise, venetoclax effectively killed TP53‐M cells. Gene expression profile analysis of TP53‐M cells revealed a downmodulation of B‐cell receptor (BCR)‐related genes and an upmodulation of genes with anti‐apoptotic/pro‐survival activity, suggesting that the survival and proliferation of TP53‐M cells are less dependent on the BCR pathway. These observations further support the use of drug combinations for the optimal management of TP53‐M CLL patients. [ABSTRACT FROM AUTHOR]