FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2520339276> ?p ?o ?g. }

• W2520339276 endingPage "1257" @default.
• W2520339276 startingPage "1248" @default.
• W2520339276 abstract "Abstract A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)–persistent leukemic stem cells (LSC). These are BCR–ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i). EZH2i does not impair normal hematopoietic stem cell survival. Strikingly, treatment of primary CML cells with either EZH2i or TKI alone caused significant upregulation of H3K27me3 targets, and combined treatment further potentiated these effects and resulted in significant loss of LSCs compared to TKI alone, in vitro, and in long-term bone marrow murine xenografts. Our findings point to a promising epigenetic-based therapeutic strategy to more effectively target LSCs in patients with CML receiving TKIs. Significance: In CML, TKI-persistent LSCs remain an obstacle to cure, and approaches to eradicate them remain a significant unmet clinical need. We demonstrate that EZH2 and H3K27me3 reprogramming is important for LSC survival, but renders LSCs sensitive to the combined effects of EZH2i and TKI. This represents a novel approach to more effectively target LSCs in patients receiving TKI treatment. Cancer Discov; 6(11); 1248–57. ©2016 AACR. See related article by Xie et al., p. 1237. This article is highlighted in the In This Issue feature, p. 1197" @default.
• W2520339276 created "2016-09-23" @default.
• W2520339276 creator A5004158727 @default.
• W2520339276 creator A5014762019 @default.
• W2520339276 creator A5018919552 @default.
• W2520339276 creator A5020420655 @default.
• W2520339276 creator A5027820599 @default.
• W2520339276 creator A5032156036 @default.
• W2520339276 creator A5038233525 @default.
• W2520339276 creator A5042952004 @default.
• W2520339276 creator A5045823910 @default.
• W2520339276 creator A5047711932 @default.
• W2520339276 creator A5047732858 @default.
• W2520339276 creator A5053053373 @default.
• W2520339276 creator A5056802730 @default.
• W2520339276 creator A5064719006 @default.
• W2520339276 creator A5069956148 @default.
• W2520339276 creator A5085091768 @default.
• W2520339276 creator A5087500042 @default.
• W2520339276 date "2016-11-01" @default.
• W2520339276 modified "2023-10-12" @default.
• W2520339276 title "Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition" @default.
• W2520339276 cites W120597284 @default.
• W2520339276 cites W1963736125 @default.
• W2520339276 cites W1964280661 @default.
• W2520339276 cites W1976515482 @default.
• W2520339276 cites W1977199336 @default.
• W2520339276 cites W1981122980 @default.
• W2520339276 cites W1990646351 @default.
• W2520339276 cites W2013307916 @default.
• W2520339276 cites W2027877663 @default.
• W2520339276 cites W2037837200 @default.
• W2520339276 cites W2055302801 @default.
• W2520339276 cites W2058261916 @default.
• W2520339276 cites W2060608189 @default.
• W2520339276 cites W2062166095 @default.
• W2520339276 cites W2062390094 @default.
• W2520339276 cites W2064367288 @default.
• W2520339276 cites W2069444276 @default.
• W2520339276 cites W2086376086 @default.
• W2520339276 cites W2100630390 @default.
• W2520339276 cites W2112817157 @default.
• W2520339276 cites W2122224021 @default.
• W2520339276 cites W2127282739 @default.
• W2520339276 cites W2142188454 @default.
• W2520339276 cites W2150926065 @default.
• W2520339276 cites W2157501125 @default.
• W2520339276 cites W2519014907 @default.
• W2520339276 cites W4253812362 @default.
• W2520339276 doi "https://doi.org/10.1158/2159-8290.cd-16-0263" @default.
• W2520339276 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6538532" @default.
• W2520339276 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27630125" @default.
• W2520339276 hasPublicationYear "2016" @default.
• W2520339276 type Work @default.
• W2520339276 sameAs 2520339276 @default.
• W2520339276 citedByCount "97" @default.
• W2520339276 countsByYear W25203392762016 @default.
• W2520339276 countsByYear W25203392762017 @default.
• W2520339276 countsByYear W25203392762018 @default.
• W2520339276 countsByYear W25203392762019 @default.
• W2520339276 countsByYear W25203392762020 @default.
• W2520339276 countsByYear W25203392762021 @default.
• W2520339276 countsByYear W25203392762022 @default.
• W2520339276 countsByYear W25203392762023 @default.
• W2520339276 crossrefType "journal-article" @default.
• W2520339276 hasAuthorship W2520339276A5004158727 @default.
• W2520339276 hasAuthorship W2520339276A5014762019 @default.
• W2520339276 hasAuthorship W2520339276A5018919552 @default.
• W2520339276 hasAuthorship W2520339276A5020420655 @default.
• W2520339276 hasAuthorship W2520339276A5027820599 @default.
• W2520339276 hasAuthorship W2520339276A5032156036 @default.
• W2520339276 hasAuthorship W2520339276A5038233525 @default.
• W2520339276 hasAuthorship W2520339276A5042952004 @default.
• W2520339276 hasAuthorship W2520339276A5045823910 @default.
• W2520339276 hasAuthorship W2520339276A5047711932 @default.
• W2520339276 hasAuthorship W2520339276A5047732858 @default.
• W2520339276 hasAuthorship W2520339276A5053053373 @default.
• W2520339276 hasAuthorship W2520339276A5056802730 @default.
• W2520339276 hasAuthorship W2520339276A5064719006 @default.
• W2520339276 hasAuthorship W2520339276A5069956148 @default.
• W2520339276 hasAuthorship W2520339276A5085091768 @default.
• W2520339276 hasAuthorship W2520339276A5087500042 @default.
• W2520339276 hasBestOaLocation W25203392761 @default.
• W2520339276 hasConcept C104317684 @default.
• W2520339276 hasConcept C109159458 @default.
• W2520339276 hasConcept C121608353 @default.
• W2520339276 hasConcept C126322002 @default.
• W2520339276 hasConcept C1491633281 @default.
• W2520339276 hasConcept C170493617 @default.
• W2520339276 hasConcept C203014093 @default.
• W2520339276 hasConcept C2778820342 @default.
• W2520339276 hasConcept C28328180 @default.
• W2520339276 hasConcept C41091548 @default.
• W2520339276 hasConcept C42362537 @default.
• W2520339276 hasConcept C50171091 @default.
• W2520339276 hasConcept C502942594 @default.
• W2520339276 hasConcept C54355233 @default.
• W2520339276 hasConcept C55493867 @default.

• next