NDLI: Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia

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Targeting of HSP70/HSF1 Axis Abrogates In Vitro Ibrutinib-Resistance in Chronic Lymphocytic Leukemia

Content Provider	MDPI
Author	Frezzato, Federica Visentin, Andrea Severin, Filippo Pizzo, Serena Ruggeri, Edoardo Mouawad, Nayla Martinello, Leonardo Pagnin, Elisa Trimarco, Valentina Tonini, Alessia Carraro, Samuel A. Pravato, Stefano Imbergamo, Silvia Manni, Sabrina Piazza, Francesco Brunati, Anna Maria Facco, Monica Trentin, Livio
Copyright Year	2021
Description	The Btk inhibitor ibrutinib has significantly changed the management of chronic lymphocytic leukemia (CLL) patients. Despite its clinical efficacy, relapses occur, and outcomes after ibrutinib failure are poor. Although BTK and PLCγ2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations. The heat shock protein of 70 kDa (HSP70) and its transcription factor heat shock factor 1 (HSF1) play a role in mediating the survival and progression of CLL, as well as taking part in drug resistance in various cancers. We demonstrated that resveratrol and related phenols were able to induce apoptosis in vitro in leukemic cells from CLL untreated patients by acting on the HSP70/HSF1 axis. The same was achieved in cells recovered from 13 CLL patients failing in vivo ibrutinib treatment. HSP70 and HSF1 levels decreased following in vitro treatment, correlating to apoptosis induction. We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients. The targeting of HSP70/HSF1 axis could represent a novel rational therapeutic strategy for CLL, also for relapsing patients.
Starting Page	5453
e-ISSN	20726694
DOI	10.3390/cancers13215453
Journal	Cancers
Issue Number	21
Volume Number	13
Language	English
Publisher	MDPI
Publisher Date	2021-10-29
Access Restriction	Open
Subject Keyword	Cancers Oncology Chronic Lymphocytic Leukemia Ibrutinib Hsp70 Hsf1 Drug-resistance Phenols
Content Type	Text
Resource Type	Article

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