Matches in SemOpenAlex for { <https://semopenalex.org/work/W2500133046> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W2500133046 abstract "Myeloproliferative neoplasm, myelofibrosis (MPN-MF), exhibits increased JAK-STAT signaling and often progresses (∼15-20%) to AML (sAML). JAK inhibitor (JAK-I) ruxolitinib (Rux) or standard induction chemotherapy is only modestly active against sAML, culminating in treatment-refractory relapse. Genetic alterations commonly documented in sAML include the co-occurrence of JAK2 V617F and mutant TP53. Here, we demonstrate that treatment with ARV-825 (Arvinas, Inc.), a BET (bromodomain and extraterminal) protein PROTAC (proteasome activating chimera) which degrades (through the proteasome) BET proteins by binding and recruiting E3 Ubiquitin ligase cereblon activity to them, caused efficient, and prolonged depletion of the levels of the BET protein BRD4. In contrast, treatment with the bromodomain inhibitors (BET-Is) JQ1 or OTX015 induced the levels of BRD4. ARV-825 treatment also mediated greater and more sustained attenuation than OTX-015 of the mRNA and protein expressions of BCL-xL, CDK4/6, PIM1, p-STAT5 and p-STAT3 levels, while concomitantly inducing p21 and p27 in the cultured sAML (HEL92.1.7 and SET2) cells. This correlated with high level of apoptosis in the cultured and patient-derived post-MPN-MF sAML cells, with relative sparing of the normal CD34+ progenitor cells. Compared to treatment with each agent alone, co-treatment with ARV-825 and the JAK-Is Rux (100 to 1000 nM) or pacritinib (250 to 1000 nM), was synergistically more lethal against the cultured sAML cells (CI of 10-fold resistant to ruxolitinib; HEL/JIR cells) under the in vitro selection pressure of a continuous exposure to JAK-I. Notably, compared to the parental HEL92.1.7, HEL/JIR cells were highly and collaterally sensitive to both ARV-825 and AUY922. Furthermore, co-treatment with ARV-825 and AUY922 was also synergistically lethal against HEL/JIR cells (CI Citation Format: Dyana T. Saenz, Warren C. Fiskus, Taghi Manshouri, Jing Lu, Yimin Qian, Kanak Raina, Baohua Sun, Stephanie S. Krieger, Simrit Parmar, Srdan Verstovsek, Kapil N. Bhalla. Superior lethal activity of single agent BET protein PROTAC compared to bromodomain inhibitor or in combination with JAK inhibitor against post-myelofibrosis secondary AML cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4699." @default.
- W2500133046 created "2016-08-23" @default.
- W2500133046 creator A5000534025 @default.
- W2500133046 creator A5008109253 @default.
- W2500133046 creator A5021167157 @default.
- W2500133046 creator A5026422612 @default.
- W2500133046 creator A5035267982 @default.
- W2500133046 creator A5038644541 @default.
- W2500133046 creator A5056040915 @default.
- W2500133046 creator A5062794942 @default.
- W2500133046 creator A5067678169 @default.
- W2500133046 creator A5079069209 @default.
- W2500133046 creator A5085521139 @default.
- W2500133046 date "2016-07-15" @default.
- W2500133046 modified "2023-09-24" @default.
- W2500133046 title "Abstract 4699: Superior lethal activity of single agent BET protein PROTAC compared to bromodomain inhibitor or in combination with JAK inhibitor against post-myelofibrosis secondary AML cells" @default.
- W2500133046 doi "https://doi.org/10.1158/1538-7445.am2016-4699" @default.
- W2500133046 hasPublicationYear "2016" @default.
- W2500133046 type Work @default.
- W2500133046 sameAs 2500133046 @default.
- W2500133046 citedByCount "0" @default.
- W2500133046 crossrefType "proceedings-article" @default.
- W2500133046 hasAuthorship W2500133046A5000534025 @default.
- W2500133046 hasAuthorship W2500133046A5008109253 @default.
- W2500133046 hasAuthorship W2500133046A5021167157 @default.
- W2500133046 hasAuthorship W2500133046A5026422612 @default.
- W2500133046 hasAuthorship W2500133046A5035267982 @default.
- W2500133046 hasAuthorship W2500133046A5038644541 @default.
- W2500133046 hasAuthorship W2500133046A5056040915 @default.
- W2500133046 hasAuthorship W2500133046A5062794942 @default.
- W2500133046 hasAuthorship W2500133046A5067678169 @default.
- W2500133046 hasAuthorship W2500133046A5079069209 @default.
- W2500133046 hasAuthorship W2500133046A5085521139 @default.
- W2500133046 hasConcept C104317684 @default.
- W2500133046 hasConcept C126322002 @default.
- W2500133046 hasConcept C27740335 @default.
- W2500133046 hasConcept C2776112149 @default.
- W2500133046 hasConcept C2778305200 @default.
- W2500133046 hasConcept C2778367456 @default.
- W2500133046 hasConcept C2780007613 @default.
- W2500133046 hasConcept C2780076729 @default.
- W2500133046 hasConcept C2780862049 @default.
- W2500133046 hasConcept C2781462825 @default.
- W2500133046 hasConcept C41091548 @default.
- W2500133046 hasConcept C502942594 @default.
- W2500133046 hasConcept C55493867 @default.
- W2500133046 hasConcept C64927066 @default.
- W2500133046 hasConcept C71924100 @default.
- W2500133046 hasConcept C74401373 @default.
- W2500133046 hasConcept C86803240 @default.
- W2500133046 hasConcept C95444343 @default.
- W2500133046 hasConceptScore W2500133046C104317684 @default.
- W2500133046 hasConceptScore W2500133046C126322002 @default.
- W2500133046 hasConceptScore W2500133046C27740335 @default.
- W2500133046 hasConceptScore W2500133046C2776112149 @default.
- W2500133046 hasConceptScore W2500133046C2778305200 @default.
- W2500133046 hasConceptScore W2500133046C2778367456 @default.
- W2500133046 hasConceptScore W2500133046C2780007613 @default.
- W2500133046 hasConceptScore W2500133046C2780076729 @default.
- W2500133046 hasConceptScore W2500133046C2780862049 @default.
- W2500133046 hasConceptScore W2500133046C2781462825 @default.
- W2500133046 hasConceptScore W2500133046C41091548 @default.
- W2500133046 hasConceptScore W2500133046C502942594 @default.
- W2500133046 hasConceptScore W2500133046C55493867 @default.
- W2500133046 hasConceptScore W2500133046C64927066 @default.
- W2500133046 hasConceptScore W2500133046C71924100 @default.
- W2500133046 hasConceptScore W2500133046C74401373 @default.
- W2500133046 hasConceptScore W2500133046C86803240 @default.
- W2500133046 hasConceptScore W2500133046C95444343 @default.
- W2500133046 hasLocation W25001330461 @default.
- W2500133046 hasOpenAccess W2500133046 @default.
- W2500133046 hasPrimaryLocation W25001330461 @default.
- W2500133046 hasRelatedWork W1601101287 @default.
- W2500133046 hasRelatedWork W1973985738 @default.
- W2500133046 hasRelatedWork W2173572713 @default.
- W2500133046 hasRelatedWork W2269148561 @default.
- W2500133046 hasRelatedWork W2341810480 @default.
- W2500133046 hasRelatedWork W2521450409 @default.
- W2500133046 hasRelatedWork W2564869076 @default.
- W2500133046 hasRelatedWork W2576863267 @default.
- W2500133046 hasRelatedWork W2587172576 @default.
- W2500133046 hasRelatedWork W2589196241 @default.
- W2500133046 hasRelatedWork W2742058366 @default.
- W2500133046 hasRelatedWork W2954477621 @default.
- W2500133046 hasRelatedWork W2979312664 @default.
- W2500133046 hasRelatedWork W2979424271 @default.
- W2500133046 hasRelatedWork W2979662023 @default.
- W2500133046 hasRelatedWork W2979841932 @default.
- W2500133046 hasRelatedWork W2979996329 @default.
- W2500133046 hasRelatedWork W2980179997 @default.
- W2500133046 hasRelatedWork W2981008324 @default.
- W2500133046 hasRelatedWork W3005443003 @default.
- W2500133046 isParatext "false" @default.
- W2500133046 isRetracted "false" @default.
- W2500133046 magId "2500133046" @default.
- W2500133046 workType "article" @default.