FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3202792386> ?p ?o ?g. }

• W3202792386 abstract "Background: Acute megakaryocytic leukemia (AMKL) is a clinically heterogeneous subtype of acute myeloid leukemia (AML) characterized by unrestricted megakaryoblast proliferation, myelofibrosis, and poor prognosis. Aberrant c-Mpl signaling has been implicated in a myriad of myeloid proliferative disorders, some of which can lead to AMKL, however the role of c-Mpl in AMKL progression remains largely unexplored.Methods: Quantitative real-time PCR and Western blot were carried out to identify the expression of c-Mpl variants. The binding affinities of c-Mpl to TPO and c-Mpl dimerization were investigated by surface plasmon resonance, microscale thermophoresis, and fluorescence resonance energy transfer. RNA-Seq, Co-IP, and Western blot were performed to examine the functional mechanism of c-Mpl variants in AMKL development and chemotherapy response.Finding: We identified increased expression of a c-Mpl isoform (c-Mpl-del) in the bone marrow of AMKL patients and AMKL cell lines. c-Mpl-del overexpression was correlated with enhanced AMKL cell proliferation and chemotherapeutic resistance, and decreased survival in xenografted mice. Interestingly, c-Mpl-del exhibits decreased receptor internalization resulting in increased surface stability and allowed for sustained TPO signaling. These led to the preferential phosphorylated c-Mpl-del C-terminus Y607 and biased activation of PI3K/AKT pathway, which culminated in downregulation of DDIT3-related apoptotic responses conducive to AMKL survival and proliferation.Interpretation: This study elucidates a novel role of c-Mpl in AMKL progression and drug resistance, which not only improves our understanding of c-Mpl-dependent leukemia development, but also has important implications in prognosis and treatment of AMKL.Funding: A full list of funding can be found in the Acknowledgments section.Declaration of Interest: All authors declare that they have no conflict of interest.Ethical Approval: All clinical samples were obtained with informed consent from Sun Yat-sen University Cancer Center and approved by the Hospital’s Ethical Review Committees. The animal studies were authorized by the Animal Ethic Review Committees of the Sun Yat-sen University." @default.
• W3202792386 created "2021-10-11" @default.
• W3202792386 creator A5001292694 @default.
• W3202792386 creator A5003498128 @default.
• W3202792386 creator A5005228021 @default.
• W3202792386 creator A5009513811 @default.
• W3202792386 creator A5010157362 @default.
• W3202792386 creator A5019294625 @default.
• W3202792386 creator A5024698709 @default.
• W3202792386 creator A5025582303 @default.
• W3202792386 creator A5025851882 @default.
• W3202792386 creator A5037335239 @default.
• W3202792386 creator A5049939550 @default.
• W3202792386 creator A5050268815 @default.
• W3202792386 creator A5058131413 @default.
• W3202792386 creator A5060467088 @default.
• W3202792386 creator A5062493663 @default.
• W3202792386 creator A5065573440 @default.
• W3202792386 creator A5066716873 @default.
• W3202792386 creator A5066983848 @default.
• W3202792386 creator A5068743757 @default.
• W3202792386 creator A5072950258 @default.
• W3202792386 creator A5073340607 @default.
• W3202792386 creator A5074642572 @default.
• W3202792386 creator A5084047711 @default.
• W3202792386 date "2021-01-01" @default.
• W3202792386 modified "2023-10-18" @default.
• W3202792386 title "c-Mpl-del, an Alternative Splicing Isoform of c-Mpl, Promotes Malignancy and Chemoresistance of AMKL by Regulating AKT/DDIT3 Survival Signaling" @default.
• W3202792386 cites W1525509607 @default.
• W3202792386 cites W1697828529 @default.
• W3202792386 cites W1919210865 @default.
• W3202792386 cites W1950612017 @default.
• W3202792386 cites W1969637800 @default.
• W3202792386 cites W1971390332 @default.
• W3202792386 cites W1972001907 @default.
• W3202792386 cites W1976386009 @default.
• W3202792386 cites W1977659503 @default.
• W3202792386 cites W1983612778 @default.
• W3202792386 cites W1991333664 @default.
• W3202792386 cites W1992216560 @default.
• W3202792386 cites W1997632886 @default.
• W3202792386 cites W1997832862 @default.
• W3202792386 cites W2000583684 @default.
• W3202792386 cites W2000811690 @default.
• W3202792386 cites W2001388611 @default.
• W3202792386 cites W2002188783 @default.
• W3202792386 cites W2002776160 @default.
• W3202792386 cites W2014000431 @default.
• W3202792386 cites W2015806646 @default.
• W3202792386 cites W2017820635 @default.
• W3202792386 cites W2017852261 @default.
• W3202792386 cites W2018420076 @default.
• W3202792386 cites W2020948603 @default.
• W3202792386 cites W2030118761 @default.
• W3202792386 cites W2049033479 @default.
• W3202792386 cites W2052908684 @default.
• W3202792386 cites W2059741696 @default.
• W3202792386 cites W2064237737 @default.
• W3202792386 cites W2067986039 @default.
• W3202792386 cites W2076011083 @default.
• W3202792386 cites W2093758335 @default.
• W3202792386 cites W2106117938 @default.
• W3202792386 cites W2111869831 @default.
• W3202792386 cites W2112760492 @default.
• W3202792386 cites W2144887977 @default.
• W3202792386 cites W2157143174 @default.
• W3202792386 cites W2171387325 @default.
• W3202792386 cites W2178248816 @default.
• W3202792386 cites W2409342027 @default.
• W3202792386 cites W2412688330 @default.
• W3202792386 cites W2584590372 @default.
• W3202792386 cites W2586493063 @default.
• W3202792386 cites W2620184844 @default.
• W3202792386 cites W2750527120 @default.
• W3202792386 cites W2887835345 @default.
• W3202792386 cites W2937356612 @default.
• W3202792386 cites W2984017198 @default.
• W3202792386 cites W3001367168 @default.
• W3202792386 cites W3037540119 @default.
• W3202792386 cites W3045608007 @default.
• W3202792386 cites W4234605983 @default.
• W3202792386 cites W937550426 @default.
• W3202792386 doi "https://doi.org/10.2139/ssrn.3909747" @default.
• W3202792386 hasPublicationYear "2021" @default.
• W3202792386 type Work @default.
• W3202792386 sameAs 3202792386 @default.
• W3202792386 citedByCount "0" @default.
• W3202792386 crossrefType "journal-article" @default.
• W3202792386 hasAuthorship W3202792386A5001292694 @default.
• W3202792386 hasAuthorship W3202792386A5003498128 @default.
• W3202792386 hasAuthorship W3202792386A5005228021 @default.
• W3202792386 hasAuthorship W3202792386A5009513811 @default.
• W3202792386 hasAuthorship W3202792386A5010157362 @default.
• W3202792386 hasAuthorship W3202792386A5019294625 @default.
• W3202792386 hasAuthorship W3202792386A5024698709 @default.
• W3202792386 hasAuthorship W3202792386A5025582303 @default.
• W3202792386 hasAuthorship W3202792386A5025851882 @default.
• W3202792386 hasAuthorship W3202792386A5037335239 @default.
• W3202792386 hasAuthorship W3202792386A5049939550 @default.
• W3202792386 hasAuthorship W3202792386A5050268815 @default.

• next