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Unravelling the suboptimal response of TP 53 ‐mutated chronic lymphocytic leukaemia to ibrutinib
Author(s) -
Guarini Anna,
Peragine Nadia,
Messina Monica,
Marinelli Marilisa,
Ilari Caterina,
Cafforio Luciana,
Raponi Sara,
Bonina Silvia,
Mariglia Paola,
Mauro Francesca R.,
Gaidano Gianluca,
Del Giudice Ilaria,
Foà Robin
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15613
Subject(s) - ibrutinib , venetoclax , chronic lymphocytic leukemia , breakpoint cluster region , bruton's tyrosine kinase , cancer research , apoptosis , hematology , immunology , b cell receptor , phenotype , gene , biology , b cell , leukemia , receptor , medicine , oncology , antibody , tyrosine kinase , genetics
Summary TP 53 ‐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 TP 53 ‐mutated ( TP 53 ‐M) CLL cells compared to TP 53 wild‐type cells. Contrariwise, venetoclax effectively killed TP 53 ‐M cells. Gene expression profile analysis of TP 53 ‐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 TP 53 ‐M cells are less dependent on the BCR pathway. These observations further support the use of drug combinations for the optimal management of TP 53 ‐M CLL patients.