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Leukemia stem cell regulation and resistance
Organization UNIVERSITY OF ALABAMA AT BIRMINGHAMLocation BIRMINGHAM, UNITED STATESPosted 15 Feb 2021Deadline 31 Jan 2026 β οΈ
NIHUS FederalResearch GrantFY2025Active OxygenAntioncogene Protein p53BCR-ABL KinaseBasal Transcription FactorBasal transcription factor genesBcr-Abl tyrosine kinaseBiologyBlood Precursor CellBone MarrowBone Marrow Reticuloendothelial SystemCXCL12CXCL12 geneCXCL12 proteinCancersCell Communication and SignalingCell DeathCell FunctionCell PhysiologyCell ProcessCell SignalingCell SurvivalCell ViabilityCellular FunctionCellular Metabolic ProcessCellular PhysiologyCellular ProcessCellular Tumor Antigen P53Chemokine (C-X-C Motif) Ligand 12Chronic Granulocytic LeukemiaChronic Myelocytic LeukemiaChronic Myelogenous LeukemiaChronic Myeloid LeukemiaD-GlucoseDeacetylaseDeacetylationDevelopmentDextroseDiseaseDisease remissionDisorderDrug resistanceEPH- and ELK-Related Tyrosine KinaseEPH-and ELK-Related KinaseEphrin Type-A Receptor 8Ephrin Type-A Receptor 8 PrecursorFatty AcidsFinancial HardshipGene CombinationsGene ExpressionGeneral Transcription Factor GeneGeneral Transcription FactorsGenerationsGlnGlucoseGlutamineGlycolysisGoalsHSC quiescenceHematologic CancerHematologic MalignanciesHematologic NeoplasmsHematological MalignanciesHematological NeoplasmsHematological TumorHematopoietic CancerHematopoietic Progenitor CellsHematopoietic stem cellsIn VitroIntermediary MetabolismIntracellular Communication and SignalingKnowledgeL-GlutamineLabelLeukemic progenitor and stem cellMaintenanceMalignant Hematologic NeoplasmMalignant NeoplasmsMalignant TumorMesenchymal Progenitor CellMesenchymal Stem CellsMesenchymal progenitorMesenchymal stromal/stem cellsMetabolicMetabolic PathwayMetabolic ProcessesMetabolismMitochondriaMitochondrial ProteinsNatural regenerationOncoprotein p53Oxidative PhosphorylationOxidative Phosphorylation PathwayOxygen RadicalsP53PBSFPPAR alphaPPAR-Ξ±PPARalphaPPARΞ±PTK InhibitorsPatientsPeroxisome Proliferator-Activated Receptor alphaPeroxisome Proliferator-Activated Receptor Ξ±Phosphoprotein P53Phosphoprotein pp53PlayPre-B Cell Growth Stimulating FactorPro-OxidantsProcessProliferatingProtein TP53Protein Tyrosine KinaseProtein Tyrosine Kinase EEKProtein Tyrosine Kinase InhibitorsQ LevoglutamideQ. LevoglutamideReactive Oxygen SpeciesRegenerationRegulationRelapseRemissionRemission InductionResearchResistanceRespirationRiskRoleSCYB12SDF-1SDF-1ASDF-1BSDF-1alphaSDF1SDF1ASDF1BSIRT1SIRT1 geneSdf1 proteinSignal TransductionSignal Transduction SystemsSignalingSirtuin 1Stromal Cell-Derived Factor 1Subcellular ProcessTK InhibitorsTLSF-ATLSF-BTP53TP53 geneTPAR1TRP53Toxic effectToxicitiesTranscription ActivatorTranscription CoactivatorTranscription Factor CoactivatorTranscription Factor Proto-OncogeneTranscription factor genesTranscriptional Activator/CoactivatorTranslationsTumor Protein p53Tumor Protein p53 GeneTyrosine KinaseTyrosine Kinase InhibitorTyrosine-Protein Kinase Receptor EEKTyrosine-Specific Protein KinaseTyrosylprotein Kinasebiological signal transductionblood cell progenitorblood progenitorblood stem cellblood stem cell quiescenceblood-forming stem cellcell metabolismcell transformationcellular metabaolismcofactordevelopmentaldrug resistantextracellularfatty acid oxidationfinancial adversityfinancial burdenfinancial distressfinancial insecurityfinancial strainfinancial stresshIRHhematopoietic progenitorhematopoietic stem cell quiescencehematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellhydroxyaryl protein kinaseimprovedimproved outcomein vivoinhibitorleukemialeukemia stem/initiating cellsleukemia treatmentleukemic progenitorleukemic stem cellleukemic therapymalignancymesenchymal stromal cellmesenchymal stromal progenitor cellsmesenchymal-derived stem cellsmitochondrialmitochondrial metabolismnecrocytosisneoplasm/cancernew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetoverexpressoverexpressionoxidationp53 Antigenp53 Genesp53 Tumor Suppressorpreservationprogenitor Cell growthprogenitor cell fateprogenitor cell functionprogenitor cell maintenanceprogenitor cell poolprogenitor cell populationprogenitor fateprogenitor functionprogenitor growthprogenitor maintenanceprogenitor poolprogenitor populationprotein p53regenerateresistance to Drugresistance to therapyresistantresistant to Drugresistant to therapyrespiratory mechanismresponserestorationself-renewself-renewalsocial rolestem and progenitor cell fatestem and progenitor cell functionstem and progenitor cell populationstem and progenitor functionstem cell fatestem cell functionstem cell growthstem cell maintenancestem cell poolstem cell populationstromal cell-derived factor-1alphatargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic resistancetherapy resistanttranscription factortransformed cellstranslationtreatment resistancetyrosyl protein kinase
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PROJECT SUMMARY/ABSTRACT
Chronic myelogenous leukemia (CML) results from hematopoietic stem cell (HSC) transformation by the BCR-
ABL tyrosine kinase. Tyrosine kinase inhibitors (TKI) are effective in inducing remission and prolonging survival
in CML patients, but fail to eliminate primitive leukemia stem cells (LSC) that can regenerate disease.β¦
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