Matches in SemOpenAlex for { <https://semopenalex.org/work/W4229456253> ?p ?o ?g. }
- W4229456253 abstract "Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of MEF2C expression in patients with ETP-ALL. Using both in vivo and in vitro models of ETP-ALL, we demonstrate that elevated MEF2C expression blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. MEF2C activates a B cell transcriptional program in addition to RUNX1, GATA3, and LMO2; upregulates the IL-7R; and boosts cell survival by upregulation of BCL2. MEF2C and the Notch pathway, therefore, demarcate opposite regulators of B- or T-lineage choices, respectively. Enforced MEF2C expression in mouse or human progenitor cells effectively blocks early T cell differentiation and promotes the development of biphenotypic lymphoid tumors that coexpress CD3 and CD19, resembling human mixed phenotype acute leukemia. Salt-inducible kinase (SIK) inhibitors impair MEF2C activity and alleviate the T cell developmental block. Importantly, this sensitizes cells to prednisolone treatment. Therefore, SIK-inhibiting compounds such as dasatinib are potentially valuable additions to standard chemotherapy for human ETP-ALL." @default.
- W4229456253 created "2022-05-11" @default.
- W4229456253 creator A5010644426 @default.
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- W4229456253 creator A5091646302 @default.
- W4229456253 date "2022-07-08" @default.
- W4229456253 modified "2023-09-27" @default.
- W4229456253 title "MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus" @default.
- W4229456253 cites W1487236491 @default.
- W4229456253 cites W1552816596 @default.
- W4229456253 cites W1578561002 @default.
- W4229456253 cites W1766090917 @default.
- W4229456253 cites W1900565974 @default.
- W4229456253 cites W1940642564 @default.
- W4229456253 cites W1967609586 @default.
- W4229456253 cites W1976955442 @default.
- W4229456253 cites W1989838840 @default.
- W4229456253 cites W1990147363 @default.
- W4229456253 cites W1992644927 @default.
- W4229456253 cites W1992714205 @default.
- W4229456253 cites W1994791278 @default.
- W4229456253 cites W1996258482 @default.
- W4229456253 cites W1997565067 @default.
- W4229456253 cites W2000589976 @default.
- W4229456253 cites W2003452068 @default.
- W4229456253 cites W200461798 @default.
- W4229456253 cites W2008340135 @default.
- W4229456253 cites W2009596701 @default.
- W4229456253 cites W2011497780 @default.
- W4229456253 cites W2021341670 @default.
- W4229456253 cites W2021539006 @default.
- W4229456253 cites W2022969625 @default.
- W4229456253 cites W2028885330 @default.
- W4229456253 cites W2039616075 @default.
- W4229456253 cites W2042396121 @default.
- W4229456253 cites W2046790140 @default.
- W4229456253 cites W2048591984 @default.
- W4229456253 cites W2049396238 @default.
- W4229456253 cites W2053813270 @default.
- W4229456253 cites W2060605982 @default.
- W4229456253 cites W2067143990 @default.
- W4229456253 cites W2068980965 @default.
- W4229456253 cites W2072387160 @default.
- W4229456253 cites W2082565074 @default.
- W4229456253 cites W2086141457 @default.
- W4229456253 cites W2086525709 @default.
- W4229456253 cites W2087369559 @default.
- W4229456253 cites W2096885745 @default.
- W4229456253 cites W2102619694 @default.
- W4229456253 cites W2103177920 @default.
- W4229456253 cites W2103420336 @default.
- W4229456253 cites W2109336877 @default.
- W4229456253 cites W2109350221 @default.
- W4229456253 cites W2112431248 @default.
- W4229456253 cites W2113223926 @default.
- W4229456253 cites W2114969589 @default.
- W4229456253 cites W2116634113 @default.
- W4229456253 cites W2117813626 @default.
- W4229456253 cites W2119522973 @default.
- W4229456253 cites W2122140726 @default.
- W4229456253 cites W2128160901 @default.
- W4229456253 cites W2131607964 @default.
- W4229456253 cites W2132149459 @default.
- W4229456253 cites W2133657835 @default.
- W4229456253 cites W2135763107 @default.
- W4229456253 cites W2137797307 @default.
- W4229456253 cites W2142226489 @default.
- W4229456253 cites W2144036085 @default.
- W4229456253 cites W2146512944 @default.
- W4229456253 cites W2148839219 @default.
- W4229456253 cites W2153522676 @default.
- W4229456253 cites W2157952888 @default.
- W4229456253 cites W2166021986 @default.
- W4229456253 cites W2166306614 @default.
- W4229456253 cites W2169187666 @default.
- W4229456253 cites W2170505338 @default.
- W4229456253 cites W2198353771 @default.
- W4229456253 cites W2209200250 @default.
- W4229456253 cites W2288518003 @default.
- W4229456253 cites W2312705855 @default.
- W4229456253 cites W2336673742 @default.
- W4229456253 cites W2339215362 @default.
- W4229456253 cites W2341539131 @default.
- W4229456253 cites W2439943347 @default.
- W4229456253 cites W2479754410 @default.
- W4229456253 cites W2567340698 @default.
- W4229456253 cites W2576582957 @default.
- W4229456253 cites W2590323980 @default.
- W4229456253 cites W2593494308 @default.