Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.1925
DC Field | Value | |
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dc.title | The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors | |
dc.contributor.author | Ko T.K. | |
dc.contributor.author | Chuah C.T. | |
dc.contributor.author | Huang J.W. | |
dc.contributor.author | Ng K.-P. | |
dc.contributor.author | Ong S.T. | |
dc.date.accessioned | 2020-09-03T10:41:23Z | |
dc.date.available | 2020-09-03T10:41:23Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Ko T.K., Chuah C.T., Huang J.W., Ng K.-P., Ong S.T. (2014). The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors. Oncotarget 5 (19) : 9033-9038. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.1925 | |
dc.identifier.issn | 19492553 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/174163 | |
dc.description.abstract | BCR-ABL1-specific tyrosine kinase inhibitors prolong the life of patients with chronic myeloid leukemia (CML) but cannot completely eradicate CML progenitors. The BH3 mimetic, ABT-263, targets prosurvival BCL2 family members, and has activity against CML progenitors. However, the inhibitory effect of ABT-263 on BCL-XL, which mediates platelet survival, produces dose-limiting thrombocytopenia. A second-generation BH3 mimetic, ABT-199, has been developed to specifically bind BCL2 but not BCL-XL. We determined the activity of ABT-199 against CML cell lines, as well as primary CML and normal cord blood (NCB) progenitors. We find that BCL2 expression levels predict sensitivity to ABT-199 in CML and NCB progenitors, and that high NCB BCL2 levels may explain the reported hematologic toxicities in ABT-199-treated patients. Also, while single agent ABT-199 has modest activity against CML progenitors, when combined with imatinib, ABT-199 significantly enhances imatinib activity against CML progenitors at concentrations predicted to avoid hematologic toxicities. | |
dc.source | Unpaywall 20200831 | |
dc.subject | BCR ABL protein | |
dc.subject | BH3 protein | |
dc.subject | imatinib | |
dc.subject | navitoclax | |
dc.subject | protein bcl 2 | |
dc.subject | protein bcl xl | |
dc.subject | protein tyrosine kinase inhibitor | |
dc.subject | venetoclax | |
dc.subject | 4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino)phenyl)sulfonyl)-2-(1H-pyrrolo(2,3-b)pyridin-5-yloxy)benzamide | |
dc.subject | aniline derivative | |
dc.subject | antineoplastic agent | |
dc.subject | benzamide derivative | |
dc.subject | fused heterocyclic rings | |
dc.subject | imatinib | |
dc.subject | navitoclax | |
dc.subject | piperazine derivative | |
dc.subject | protein bcl 2 | |
dc.subject | protein kinase inhibitor | |
dc.subject | pyrimidine derivative | |
dc.subject | sulfonamide | |
dc.subject | Article | |
dc.subject | blood toxicity | |
dc.subject | cell death | |
dc.subject | chronic myeloid leukemia | |
dc.subject | drug activity | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | IC50 | |
dc.subject | maximum tolerated dose | |
dc.subject | protein expression | |
dc.subject | thrombocyte lifespan | |
dc.subject | thrombocytopenia | |
dc.subject | antagonists and inhibitors | |
dc.subject | apoptosis | |
dc.subject | cancer stem cell | |
dc.subject | drug effects | |
dc.subject | drug resistance | |
dc.subject | drug screening | |
dc.subject | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | |
dc.subject | metabolism | |
dc.subject | tumor cell line | |
dc.subject | Aniline Compounds | |
dc.subject | Antineoplastic Agents | |
dc.subject | Apoptosis | |
dc.subject | Benzamides | |
dc.subject | Bicyclo Compounds, Heterocyclic | |
dc.subject | Cell Line, Tumor | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Humans | |
dc.subject | Imatinib Mesylate | |
dc.subject | Leukemia, Myelogenous, Chronic, BCR-ABL Positive | |
dc.subject | Neoplastic Stem Cells | |
dc.subject | Piperazines | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Proto-Oncogene Proteins c-bcl-2 | |
dc.subject | Pyrimidines | |
dc.subject | Sulfonamides | |
dc.subject | Tumor Stem Cell Assay | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.18632/oncotarget.1925 | |
dc.description.sourcetitle | Oncotarget | |
dc.description.volume | 5 | |
dc.description.issue | 19 | |
dc.description.page | 9033-9038 | |
Appears in Collections: | Elements Staff Publications |
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