Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies

The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected pervasive aberrant splicing as a characteristic feature of chronic lymphocytic leukemia (CLL), irrespective of splicing factor mutation status, which was asso...

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Veröffentlicht in:	JCI insight 2018-10, Vol.3 (19)
Hauptverfasser:	Ten Hacken, Elisa, Valentin, Rebecca, Regis, Fara Faye D, Sun, Jing, Yin, Shanye, Werner, Lillian, Deng, Jing, Gruber, Michaela, Wong, Jessica, Zheng, Mei, Gill, Amy L, Seiler, Michael, Smith, Peter, Thomas, Michael, Buonamici, Silvia, Ghia, Emanuela M, Kim, Ekaterina, Rassenti, Laura Z, Burger, Jan A, Kipps, Thomas J, Meyerson, Matthew L, Bachireddy, Pavan, Wang, Lili, Reed, Robin, Neuberg, Donna, Carrasco, Ruben D, Brooks, Angela N, Letai, Anthony, Davids, Matthew S, Wu, Catherine J
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Aged Aged, 80 and over Alternative Splicing - drug effects Animals Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis - drug effects Apoptosis - genetics Bridged Bicyclo Compounds, Heterocyclic - pharmacology Bridged Bicyclo Compounds, Heterocyclic - therapeutic use Disease Models, Animal Drug Resistance, Neoplasm - drug effects Drug Resistance, Neoplasm - genetics Drug Screening Assays, Antitumor Epoxy Compounds - pharmacology Epoxy Compounds - therapeutic use Female Humans Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - pathology Macrolides - pharmacology Macrolides - therapeutic use Male Mice Mice, Transgenic Middle Aged Mitochondria - drug effects Mitochondria - pathology Mutation Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors Myeloid Cell Leukemia Sequence 1 Protein - metabolism Phosphoproteins - genetics Primary Cell Culture Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors Proto-Oncogene Proteins c-bcl-2 - metabolism Pyrimidines - pharmacology Pyrimidines - therapeutic use RNA Splicing Factors - genetics Spliceosomes - drug effects Spliceosomes - metabolism Sulfonamides - pharmacology Sulfonamides - therapeutic use Thiophenes - pharmacology Thiophenes - therapeutic use
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