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Frontiers | Notch2 Increases the Resistance to Venetoclax-Induced Apoptosis in Chronic Lymphocytic Leukemia B Cells by Inducing Mcl-1

Chronic lymphocytic leukemia (CLL) has experienced a clinical revolution thanks to the discovery of crucial pathogenetic mechanisms. CLL is still an incurable disease due to intrinsic or acquired resistance of the leukemic clone. Venetoclax is a Bcl-2 inhibitor with a marked activity in CLL, but emerging patterns of resistance are being described. We hypothesize that intrinsic features of CLL cells may contribute to drive mechanisms of resistance to venetoclax. We analyzed the expression of IRF4, Notch2 and Mcl-1 in a cohort of CLL patients. We evaluated CLL cells viability after genetic and pharmaceutical modulation of Notch2 expression in patients harboring trisomy 12. We tested venetoclax in trisomy 12 CLL cells either silenced or not for Notch2 expression or in combination with an inhibitor of Mcl-1, AMG-176. Trisomy 12 CLL cells were characterized by low expression of IRF4 associated with high levels of Notch2 and Mcl-1. Notch2 and Mcl-1 expression determined protection of CLL cel ....

United States , Eteläuomen Läi , Menlo Park , Uppsala Lan , Landskapet Birkaland , Italy General , San Diego , Fondazione Cariplo , Ricerca Sul Cancro , Associazione Italiana , Progetto Eccellenza , Stefania Benatti , Fondazione Umberto Veronesi , Nucleofector Lonza , Comitato Etico Provinciale , Gilead Sciences , Becton Dickinson , Associates With Nodal Presentation , Image Lab Software , Flowjo Software , Division Of Hematology Modena , Deletion Accelerates Chronic Lymphocytic Leukemia Development , Late Germinal Center Differentiation , Subsequent Development Of Lymphadenopathy , Ge Healthcare , Tumor Protein ,

Data at AACR Demonstrate Growing Clinical Utility of Guardant Health Liquid Biopsies in the Treatmen


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10-Apr-2021
Data at AACR Demonstrate Growing Clinical Utility of Guardant Health Liquid Biopsies in the Treatment and Management of Advanced Cancers
Phase 2 trial of Amgen’s investigational KRAS
G12C inhibitor, sotorasib, demonstrated comparable efficacy between patients identified as KRAS
G12C positive using Guardant360 CDx liquid biopsy or tissue biopsy
REDWOOD CITY, Calif. (BUSINESS WIRE) Guardant Health, Inc. (Nasdaq: GH), along with leading academic institutions and pharmaceutical companies, presents new data at the AACR Virtual Annual Meeting I, April 10-15, 2021, highlighting the use of the company’s proprietary blood tests to advance precision oncology.
Key findings demonstrate the value of Guardant360 ....

San Antonio , United States , Helmy Eltoukhy , Philipz Brohawn , Carrie Mendivil , Trastuzumab Deruxtecan , Exchange Commission , Guardant Health Inc , Guardant Health , Darryl Sleep , Therapeutic Benefit , Financial Condition , Annual Report , Quarterly Report , Bladder Cancer Treated , Clin Cancer Res , Clin Oncol , Antonio Breast Cancer Virtual Symposium , Cancer Res , Patients With , Low Expressing Advanced Breast Cancer , Results From , Predictive Impact , Circulating Tumor , Advanced Cancers Treated , Immune Checkpoint ,