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Unravelling the suboptimal response of TP53-mutated chronic lymphocytic leukaemia to ibrutinib.
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.
Affiliation
  • Guarini A; Department of Molecular Medicine, "Sapienza" University, Rome, Italy.
  • Peragine N; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Messina M; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Marinelli M; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Ilari C; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Cafforio L; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Raponi S; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Bonina S; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Mariglia P; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Mauro FR; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Gaidano G; Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
  • Del Giudice I; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
  • Foà R; Department of Cellular Biotechnologies and Haematology, "Sapienza" University, Rome, Italy.
Br J Haematol ; 184(3): 392-396, 2019 02.
Article in En | MEDLINE | ID: mdl-30338509
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.
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Full text: 1 Database: MEDLINE Main subject: Pyrazoles / Pyrimidines / Receptors, Antigen, B-Cell / Leukemia, Lymphocytic, Chronic, B-Cell / Down-Regulation / Gene Expression Regulation, Neoplastic / Tumor Suppressor Protein p53 / Mutation Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Br J Haematol Year: 2019 Type: Article Affiliation country: Italy
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Full text: 1 Database: MEDLINE Main subject: Pyrazoles / Pyrimidines / Receptors, Antigen, B-Cell / Leukemia, Lymphocytic, Chronic, B-Cell / Down-Regulation / Gene Expression Regulation, Neoplastic / Tumor Suppressor Protein p53 / Mutation Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Br J Haematol Year: 2019 Type: Article Affiliation country: Italy