Matches in SemOpenAlex for { <https://semopenalex.org/work/W2059384437> ?p ?o ?g. }
- W2059384437 endingPage "857" @default.
- W2059384437 startingPage "847" @default.
- W2059384437 abstract "Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (S ETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS." @default.
- W2059384437 created "2016-06-24" @default.
- W2059384437 creator A5002091044 @default.
- W2059384437 creator A5004007765 @default.
- W2059384437 creator A5008450550 @default.
- W2059384437 creator A5010528337 @default.
- W2059384437 creator A5011196103 @default.
- W2059384437 creator A5012953335 @default.
- W2059384437 creator A5014193228 @default.
- W2059384437 creator A5018769284 @default.
- W2059384437 creator A5019855418 @default.
- W2059384437 creator A5025595346 @default.
- W2059384437 creator A5030880015 @default.
- W2059384437 creator A5032738660 @default.
- W2059384437 creator A5033665803 @default.
- W2059384437 creator A5037524276 @default.
- W2059384437 creator A5041201931 @default.
- W2059384437 creator A5042061557 @default.
- W2059384437 creator A5054497666 @default.
- W2059384437 creator A5062110934 @default.
- W2059384437 creator A5062824446 @default.
- W2059384437 date "2014-10-13" @default.
- W2059384437 modified "2023-10-12" @default.
- W2059384437 title "SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS" @default.
- W2059384437 cites W1515392484 @default.
- W2059384437 cites W1660133344 @default.
- W2059384437 cites W1745634660 @default.
- W2059384437 cites W1965033113 @default.
- W2059384437 cites W1966783830 @default.
- W2059384437 cites W1973159660 @default.
- W2059384437 cites W1976573435 @default.
- W2059384437 cites W1976913227 @default.
- W2059384437 cites W1981083415 @default.
- W2059384437 cites W1990193106 @default.
- W2059384437 cites W1992320498 @default.
- W2059384437 cites W1993226749 @default.
- W2059384437 cites W1993236149 @default.
- W2059384437 cites W1993524489 @default.
- W2059384437 cites W1995240302 @default.
- W2059384437 cites W2000213929 @default.
- W2059384437 cites W2011813966 @default.
- W2059384437 cites W2012847858 @default.
- W2059384437 cites W2016531290 @default.
- W2059384437 cites W2025391163 @default.
- W2059384437 cites W2026134786 @default.
- W2059384437 cites W2031570299 @default.
- W2059384437 cites W2032991699 @default.
- W2059384437 cites W2047760441 @default.
- W2059384437 cites W2048865995 @default.
- W2059384437 cites W2065700140 @default.
- W2059384437 cites W2070152906 @default.
- W2059384437 cites W2070982730 @default.
- W2059384437 cites W2071183768 @default.
- W2059384437 cites W2073889874 @default.
- W2059384437 cites W2074783687 @default.
- W2059384437 cites W2076367236 @default.
- W2059384437 cites W2077038948 @default.
- W2059384437 cites W2085823469 @default.
- W2059384437 cites W2086704257 @default.
- W2059384437 cites W2090786449 @default.
- W2059384437 cites W2091242855 @default.
- W2059384437 cites W2091339057 @default.
- W2059384437 cites W2097743943 @default.
- W2059384437 cites W2109336877 @default.
- W2059384437 cites W2110909186 @default.
- W2059384437 cites W2111391000 @default.
- W2059384437 cites W2115551519 @default.
- W2059384437 cites W2116205277 @default.
- W2059384437 cites W2123355582 @default.
- W2059384437 cites W2130410032 @default.
- W2059384437 cites W2135835093 @default.
- W2059384437 cites W2135898863 @default.
- W2059384437 cites W2138122783 @default.
- W2059384437 cites W2144878135 @default.
- W2059384437 cites W2151790552 @default.
- W2059384437 cites W2159249303 @default.
- W2059384437 cites W2162937786 @default.
- W2059384437 cites W2169172058 @default.
- W2059384437 cites W2296225964 @default.
- W2059384437 cites W251630186 @default.
- W2059384437 cites W3028816248 @default.
- W2059384437 cites W4211114385 @default.
- W2059384437 cites W4237747603 @default.
- W2059384437 doi "https://doi.org/10.1038/leu.2014.301" @default.
- W2059384437 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4501574" @default.
- W2059384437 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25306901" @default.
- W2059384437 hasPublicationYear "2014" @default.
- W2059384437 type Work @default.
- W2059384437 sameAs 2059384437 @default.
- W2059384437 citedByCount "68" @default.
- W2059384437 countsByYear W20593844372014 @default.
- W2059384437 countsByYear W20593844372015 @default.
- W2059384437 countsByYear W20593844372016 @default.
- W2059384437 countsByYear W20593844372017 @default.
- W2059384437 countsByYear W20593844372018 @default.
- W2059384437 countsByYear W20593844372019 @default.
- W2059384437 countsByYear W20593844372020 @default.
- W2059384437 countsByYear W20593844372021 @default.