Please use this identifier to cite or link to this item:
https://doi.org/10.1182/blood-2009-07-235143
DC Field | Value | |
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dc.title | Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia | |
dc.contributor.author | Sanda, T | |
dc.contributor.author | Li, X | |
dc.contributor.author | Gutierrez, A | |
dc.contributor.author | Ahn, Y | |
dc.contributor.author | Neuberg, D.S | |
dc.contributor.author | O'Neil, J | |
dc.contributor.author | Strack, P.R | |
dc.contributor.author | Winter, C.G | |
dc.contributor.author | Winter, S.S | |
dc.contributor.author | Larson, R.S | |
dc.contributor.author | Von Boehmer, H | |
dc.contributor.author | Look, A.T | |
dc.date.accessioned | 2020-11-23T09:00:51Z | |
dc.date.available | 2020-11-23T09:00:51Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Sanda, T, Li, X, Gutierrez, A, Ahn, Y, Neuberg, D.S, O'Neil, J, Strack, P.R, Winter, C.G, Winter, S.S, Larson, R.S, Von Boehmer, H, Look, A.T (2010). Interconnecting molecular pathways in the pathogenesis and drug sensitivity of T-cell acute lymphoblastic leukemia. Blood 115 (9) : 1735-1745. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2009-07-235143 | |
dc.identifier.issn | 0006-4971 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/183915 | |
dc.description.abstract | To identify dysregulated pathways in distinct phases of NOTCH1-mediated T-cell leukemogenesis, as well as small-molecule inhibitors that could synergize with or substitute for ?-secretase inhibitors (GSIs) in T-cell acute lymphoblastic leukemia (T-ALL) therapy, we compared gene expression profiles in a Notch1-induced mouse model of T-ALL with those in human T-ALL. The overall patterns of NOTCH1-mediated gene expression in human and mouse T-ALLs were remarkably similar, as defined early in transformation in the mouse by the regulation of MYC and its target genes and activation of nuclear factor-?B and PI3K/AKT pathways. Later events in murine Notch1-mediated leukemogenesis included down-regulation of genes encoding tumor suppressors and negative cell cycle regulators. Gene set enrichment analysis and connectivity map algorithm predicted that small-molecule inhibitors, including heat-shock protein 90, histone deacetylase, PI3K/AKT, and proteasome inhibitors, could reverse the gene expression changes induced by NOTCH1. When tested in vitro, histone deacetylase, PI3K and proteasome inhibitors synergized with GSI in suppressing T-ALL cell growth in GSI-sensitive cells. Interestingly, alvespimycin, a potent inhibitor of the heat-shock protein 90 molecular chaperone, markedly inhibited the growth of both GSI-sensitive and -resistant T-ALL cells, suggesting that its loss disrupts signal transduction pathways crucial for the growth and survival of T-ALL cells. © 2010 by The American Society of Hematology. | |
dc.publisher | American Society of Hematology | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | alvespimycin | |
dc.subject | chaperone | |
dc.subject | gamma secretase inhibitor | |
dc.subject | heat shock protein 90 | |
dc.subject | heat shock protein 90 inhibitor | |
dc.subject | histone deacetylase | |
dc.subject | immunoglobulin enhancer binding protein | |
dc.subject | Myc protein | |
dc.subject | Notch1 receptor | |
dc.subject | phosphatidylinositol 3 kinase | |
dc.subject | proteasome inhibitor | |
dc.subject | protein kinase B | |
dc.subject | tumor suppressor protein | |
dc.subject | unclassified drug | |
dc.subject | enzyme inhibitor | |
dc.subject | NOTCH1 protein, human | |
dc.subject | Notch1 protein, mouse | |
dc.subject | secretase | |
dc.subject | acute lymphoblastic leukemia | |
dc.subject | algorithm | |
dc.subject | analysis | |
dc.subject | animal cell | |
dc.subject | animal model | |
dc.subject | article | |
dc.subject | cancer growth | |
dc.subject | cancer inhibition | |
dc.subject | cell growth | |
dc.subject | cell survival | |
dc.subject | comparative study | |
dc.subject | controlled study | |
dc.subject | down regulation | |
dc.subject | drug sensitivity | |
dc.subject | female | |
dc.subject | gene | |
dc.subject | gene expression | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | in vitro study | |
dc.subject | leukemia cell | |
dc.subject | leukemogenesis | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | nucleotide sequence | |
dc.subject | pathogenesis | |
dc.subject | prediction | |
dc.subject | priority journal | |
dc.subject | signal transduction | |
dc.subject | T lymphocyte | |
dc.subject | acute lymphoblastic leukemia | |
dc.subject | animal | |
dc.subject | cell cycle | |
dc.subject | cell proliferation | |
dc.subject | cell transformation | |
dc.subject | drug antagonism | |
dc.subject | experimental leukemia | |
dc.subject | gene expression profiling | |
dc.subject | genetics | |
dc.subject | metabolism | |
dc.subject | oncogene myc | |
dc.subject | species difference | |
dc.subject | tumor cell line | |
dc.subject | Amyloid Precursor Protein Secretases | |
dc.subject | Animals | |
dc.subject | Cell Cycle | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Proliferation | |
dc.subject | Cell Survival | |
dc.subject | Cell Transformation, Neoplastic | |
dc.subject | Down-Regulation | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Gene Expression Profiling | |
dc.subject | Genes, myc | |
dc.subject | Humans | |
dc.subject | Leukemia, Experimental | |
dc.subject | Mice | |
dc.subject | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | |
dc.subject | Receptor, Notch1 | |
dc.subject | Signal Transduction | |
dc.subject | Species Specificity | |
dc.type | Article | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1182/blood-2009-07-235143 | |
dc.description.sourcetitle | Blood | |
dc.description.volume | 115 | |
dc.description.issue | 9 | |
dc.description.page | 1735-1745 | |
dc.published.state | published | |
Appears in Collections: | Staff Publications Elements |
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