Matches in SemOpenAlex for { <https://semopenalex.org/work/W3104806681> ?p ?o ?g. }
- W3104806681 endingPage "84.e4" @default.
- W3104806681 startingPage "70" @default.
- W3104806681 abstract "Fanconi anemia (FA) is a chromosome instability syndrome with congenital abnormalities, cancer predisposition and bone marrow failure (BMF). Although hematopoietic stem and progenitor cell (HSPC) transplantation is the recommended therapy, new therapies are needed for FA patients without suitable donors. BMF in FA is caused, at least in part, by a hyperactive growth-suppressive transforming growth factor β (TGFβ) pathway, regulated by the TGFβ1, TGFβ2, and TGFβ3 ligands. Accordingly, the TGFβ pathway is an attractive therapeutic target for FA. While inhibition of TGFβ1 and TGFβ3 promotes blood cell expansion, inhibition of TGFβ2 is known to suppress hematopoiesis. Here, we report the effects of AVID200, a potent TGFβ1- and TGFβ3-specific inhibitor, on FA hematopoiesis. AVID200 promoted the survival of murine FA HSPCs in vitro. AVID200 also promoted in vitro the survival of human HSPCs from patients with FA, with the strongest effect in patients progressing to severe aplastic anemia or myelodysplastic syndrome (MDS). Previous studies have indicated that the toxic upregulation of the nonhomologous end-joining (NHEJ) pathway accounts, at least in part, for the poor growth of FA HSPCs. AVID200 downregulated the expression of NHEJ-related genes and reduced DNA damage in primary FA HSPC in vitro and in in vivo models. Collectively, AVID200 exhibits activity in FA mouse and human preclinical models. AVID200 may therefore provide a therapeutic approach to improving BMF in FA." @default.
- W3104806681 created "2020-11-23" @default.
- W3104806681 creator A5003794818 @default.
- W3104806681 creator A5009535082 @default.
- W3104806681 creator A5029542794 @default.
- W3104806681 creator A5030756793 @default.
- W3104806681 creator A5037782803 @default.
- W3104806681 creator A5042254490 @default.
- W3104806681 creator A5043442872 @default.
- W3104806681 creator A5044648110 @default.
- W3104806681 creator A5045753320 @default.
- W3104806681 creator A5051001361 @default.
- W3104806681 creator A5053508230 @default.
- W3104806681 creator A5061022456 @default.
- W3104806681 creator A5063266916 @default.
- W3104806681 creator A5064217233 @default.
- W3104806681 creator A5067712261 @default.
- W3104806681 creator A5068526533 @default.
- W3104806681 creator A5073123866 @default.
- W3104806681 creator A5077967611 @default.
- W3104806681 creator A5078588576 @default.
- W3104806681 creator A5081896929 @default.
- W3104806681 creator A5085004243 @default.
- W3104806681 date "2021-01-01" @default.
- W3104806681 modified "2023-10-12" @default.
- W3104806681 title "Inhibition of TGFβ1 and TGFβ3 promotes hematopoiesis in Fanconi anemia" @default.
- W3104806681 cites W1498451757 @default.
- W3104806681 cites W1700691315 @default.
- W3104806681 cites W1969981616 @default.
- W3104806681 cites W1980052833 @default.
- W3104806681 cites W1982957001 @default.
- W3104806681 cites W1990039985 @default.
- W3104806681 cites W1998984090 @default.
- W3104806681 cites W2001907020 @default.
- W3104806681 cites W2005567329 @default.
- W3104806681 cites W2015805015 @default.
- W3104806681 cites W2016968143 @default.
- W3104806681 cites W2024290860 @default.
- W3104806681 cites W2024446761 @default.
- W3104806681 cites W2027303624 @default.
- W3104806681 cites W2040916923 @default.
- W3104806681 cites W2044069347 @default.
- W3104806681 cites W2051493175 @default.
- W3104806681 cites W2052215590 @default.
- W3104806681 cites W2057967719 @default.
- W3104806681 cites W2084186902 @default.
- W3104806681 cites W2099735643 @default.
- W3104806681 cites W2102853816 @default.
- W3104806681 cites W2114154263 @default.
- W3104806681 cites W2116583846 @default.
- W3104806681 cites W2140740750 @default.
- W3104806681 cites W2141451936 @default.
- W3104806681 cites W2150548551 @default.
- W3104806681 cites W2152350731 @default.
- W3104806681 cites W2157988767 @default.
- W3104806681 cites W2163472474 @default.
- W3104806681 cites W2166813765 @default.
- W3104806681 cites W2167464044 @default.
- W3104806681 cites W2304766253 @default.
- W3104806681 cites W2337651628 @default.
- W3104806681 cites W2346731093 @default.
- W3104806681 cites W2536873840 @default.
- W3104806681 cites W2579367181 @default.
- W3104806681 cites W2588865924 @default.
- W3104806681 cites W2608573151 @default.
- W3104806681 cites W2608956524 @default.
- W3104806681 cites W2729105878 @default.
- W3104806681 cites W2756992092 @default.
- W3104806681 cites W2781490247 @default.
- W3104806681 cites W2781947653 @default.
- W3104806681 cites W2782308194 @default.
- W3104806681 cites W2782998495 @default.
- W3104806681 cites W2785803176 @default.
- W3104806681 cites W2792367044 @default.
- W3104806681 cites W2792572471 @default.
- W3104806681 cites W2798233554 @default.
- W3104806681 cites W2840527408 @default.
- W3104806681 cites W2883657705 @default.
- W3104806681 cites W2883664363 @default.
- W3104806681 cites W2884164644 @default.
- W3104806681 cites W2951142123 @default.
- W3104806681 doi "https://doi.org/10.1016/j.exphem.2020.11.002" @default.
- W3104806681 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33166613" @default.
- W3104806681 hasPublicationYear "2021" @default.
- W3104806681 type Work @default.
- W3104806681 sameAs 3104806681 @default.
- W3104806681 citedByCount "7" @default.
- W3104806681 countsByYear W31048066812021 @default.
- W3104806681 countsByYear W31048066812022 @default.
- W3104806681 countsByYear W31048066812023 @default.
- W3104806681 crossrefType "journal-article" @default.
- W3104806681 hasAuthorship W3104806681A5003794818 @default.
- W3104806681 hasAuthorship W3104806681A5009535082 @default.
- W3104806681 hasAuthorship W3104806681A5029542794 @default.
- W3104806681 hasAuthorship W3104806681A5030756793 @default.
- W3104806681 hasAuthorship W3104806681A5037782803 @default.
- W3104806681 hasAuthorship W3104806681A5042254490 @default.
- W3104806681 hasAuthorship W3104806681A5043442872 @default.