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• W204067244 abstract "HoxA9 is frequently overexpressed in acute myeloid leukemia, myelodysplastic syndrome and a subset of acute lymphoblastic leukemia. In mouse models, HoxA9 has been shown to promote leukemogenesis. In spite of a seemingly central role in initiating leukemia, and in acting as a cofactor to promote leukemic cell growth and survival, the mechanistic pathways altered by HoxA9 overexpression, which promote the growth and survival of leukemia, are not well defined. We have developed a stromal cell dependent model of human B-lineage ALL with conditional HoxA9 activity. The HoxA9-negative pre-B cell ALL cell line, BLIN-2, was stably transduced with a retrovirus bearing HoxA9 fused to the hormone binding domain of the human estrogen receptor. HoxA9 activity is stimulated by the addition of 4-hydroxytamoxifen to the growth medium. BLIN-2 cells have an absolute dependency on stromal cell contact for growth and survival, which permits the testing of the HoxA9 mediated effects in the context of the tumor microenvironment. Induction of HoxA9 activity in BLIN-2 resulted in increased proliferation in the absence of stromal cell support and induction of surface expression of IGF-1R. Through the use of specific IGF-1R inhibitors, we demonstrated that the proliferative response upon HoxA9 stimulation was the result of signaling through the induced IGF-1R. In addition to promoting stromal cell independent proliferation, enforced induction of HoxA9 activity promoted apoptotic resistance to stromal cell/growth factor withdrawal. Inhibition of IGF-1R signaling did not abrogate the anti-apoptotic effects of HoxA9, but did result in decreased proliferation. Models of IGF-1R typically attribute anti-apoptotic effects of IGF-1R signaling to Akt signaling, whereas the proliferative effects are mediated via the ERK pathway. No changes in Akt phosphorylation were observed in BLIN-2 cells with activated HoxA9, but levels of phospho-ERK were increased. These results are consistent with a role for HoxA9 induction of IGF-1R promoting proliferation, but not apoptotic resistance. Overall, these data indicate that enforced expression of HoxA9 in leukemia promotes proliferation via an IGF-1R dependent pathway and that HoxA9 promotes apoptotic resistance to stromal cell/growth factor withdrawal through a pathway that is independent of IGF-1R signaling." @default.
• W204067244 created "2016-06-24" @default.
• W204067244 creator A5020963783 @default.
• W204067244 date "2009-01-01" @default.
• W204067244 modified "2023-09-23" @default.
• W204067244 title "Enforced expression of HoxA9 in B-lineage ALL promotes survival and proliferation of leukemic cells" @default.
• W204067244 cites W108809021 @default.
• W204067244 cites W1231309445 @default.
• W204067244 cites W140933007 @default.
• W204067244 cites W1483872789 @default.
• W204067244 cites W1484425575 @default.
• W204067244 cites W1489123075 @default.
• W204067244 cites W1504958094 @default.
• W204067244 cites W1522396134 @default.
• W204067244 cites W1523846987 @default.
• W204067244 cites W1525783802 @default.
• W204067244 cites W154103547 @default.
• W204067244 cites W1563255069 @default.
• W204067244 cites W1583743328 @default.
• W204067244 cites W1640904418 @default.
• W204067244 cites W1719442572 @default.
• W204067244 cites W177157861 @default.
• W204067244 cites W1834944463 @default.
• W204067244 cites W1839421385 @default.
• W204067244 cites W1864684674 @default.
• W204067244 cites W1942214720 @default.
• W204067244 cites W1948328269 @default.
• W204067244 cites W1965851569 @default.
• W204067244 cites W1966889718 @default.
• W204067244 cites W1967304777 @default.
• W204067244 cites W1967376170 @default.
• W204067244 cites W1969008892 @default.
• W204067244 cites W1971721584 @default.
• W204067244 cites W1972602948 @default.
• W204067244 cites W19734691 @default.
• W204067244 cites W1976468253 @default.
• W204067244 cites W1976532923 @default.
• W204067244 cites W1979798449 @default.
• W204067244 cites W1979910254 @default.
• W204067244 cites W1980212327 @default.
• W204067244 cites W1981496258 @default.
• W204067244 cites W1983121280 @default.
• W204067244 cites W1983819045 @default.
• W204067244 cites W1984670146 @default.
• W204067244 cites W1986979976 @default.
• W204067244 cites W1987266726 @default.
• W204067244 cites W1990099538 @default.
• W204067244 cites W1991710558 @default.
• W204067244 cites W1996600754 @default.
• W204067244 cites W1998142511 @default.
• W204067244 cites W2000074832 @default.
• W204067244 cites W2000284818 @default.
• W204067244 cites W2005873549 @default.
• W204067244 cites W2009165500 @default.
• W204067244 cites W2011561214 @default.
• W204067244 cites W2014313871 @default.
• W204067244 cites W2015673732 @default.
• W204067244 cites W2016237448 @default.
• W204067244 cites W2016507620 @default.
• W204067244 cites W2018697055 @default.
• W204067244 cites W2020636054 @default.
• W204067244 cites W2020707154 @default.
• W204067244 cites W2021151686 @default.
• W204067244 cites W2022989992 @default.
• W204067244 cites W2023546573 @default.
• W204067244 cites W2025966923 @default.
• W204067244 cites W2029559050 @default.
• W204067244 cites W2030573603 @default.
• W204067244 cites W2031502815 @default.
• W204067244 cites W2036661490 @default.
• W204067244 cites W2037872087 @default.
• W204067244 cites W2043201460 @default.
• W204067244 cites W2043310375 @default.
• W204067244 cites W2043804636 @default.
• W204067244 cites W2044028282 @default.
• W204067244 cites W2044553654 @default.
• W204067244 cites W2045067988 @default.
• W204067244 cites W2045452812 @default.
• W204067244 cites W2047537929 @default.
• W204067244 cites W2047636637 @default.
• W204067244 cites W2049779681 @default.
• W204067244 cites W2051839343 @default.
• W204067244 cites W2051860641 @default.
• W204067244 cites W2052985326 @default.
• W204067244 cites W2054472394 @default.
• W204067244 cites W2055188073 @default.
• W204067244 cites W2056543048 @default.
• W204067244 cites W2057418848 @default.
• W204067244 cites W2057607894 @default.
• W204067244 cites W2057713336 @default.
• W204067244 cites W2060410507 @default.
• W204067244 cites W2063424356 @default.
• W204067244 cites W2064597799 @default.
• W204067244 cites W2064609430 @default.
• W204067244 cites W2065119107 @default.
• W204067244 cites W2067008256 @default.
• W204067244 cites W2067521115 @default.
• W204067244 cites W2068354564 @default.
• W204067244 cites W2071244728 @default.
• W204067244 cites W2071837999 @default.

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