grant
TET2-mediated epitranscriptomic regulation in leukemia microenvironment
Organization BECKMAN RESEARCH INSTITUTE/CITY OF HOPELocation DUARTE, UNITED STATESPosted 21 Sept 2023Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025AML - Acute Myeloid LeukemiaAML1AMLCR1Acute Myeloblastic LeukemiaAcute Myelocytic LeukemiaAcute Myelogenous LeukemiaApicalAssayB23BS-seqBasic ResearchBasic ScienceBindingBioassayBiologicalBiological AssayBiological FunctionBiological ProcessBiologyBisulfite-based sequencingBone MarrowBone Marrow GraftingBone Marrow Reticuloendothelial SystemBone Marrow TransplantBone Marrow TransplantationCBFA2CXC-R4CXCL12CXCL12 geneCXCL12 proteinCXCR-4CXCR4CXCR4 geneCell Communication and SignalingCell SignalingChemicalsChemokine (C-X-C Motif) Ligand 12Chemokine Receptor GeneChemoresistanceClonal ExpansionCoupledCytosineD2S201EDNADNA AlterationDNA Sequence AlterationDNA binding protein BDNA mutationDNMT3aDataDeoxyribonucleic AcidDevelopmentDioxygenasesDrug resistanceEnzyme GeneEnzymesFB22FLK2FLT3FLT3 geneFMS-like tyrosine kinase 3Fms-Related Tyrosine Kinase 3Gene TranscriptionGenetic AlterationGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationHM89HSC regenerationHSC self-renewalHSY3RRHematopoietic Cell TumorHematopoietic MalignanciesHematopoietic NeoplasmsHematopoietic Neoplasms including LymphomasHematopoietic TumorHematopoietic and Lymphoid Cell NeoplasmHematopoietic and Lymphoid NeoplasmsHomingIn VitroIntracellular Communication and SignalingInvestigationKI miceKO miceKnock-in MouseKnock-out MiceKnockout MiceKnowledgeLAP3LCR1LESTRLeukemic progenitor and stem cellLigandsMLL rearrangedMLL rearrangementMLL-AF9MLL-rearranged leukemiaMLL/AF9 AMLMaintenanceMalignant Hematopoietic NeoplasmMarrow TransplantationMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMediatingMedicalMessenger RNAMethylationMiceMice MammalsModelingModificationMolecularMolecular InteractionMurineMusMutateMutationNPMNPM1NPM1 geneNPY3RNPYRNPYRLNPYY3RNon-Polyadenylated RNANucleotidesNull MousePBSFPDX modelPEBP2A2PEBP2aBPathway interactionsPatient derived xenograftPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPlayPre-B Cell Growth Stimulating FactorPrognosisRNARNA ExpressionRNA Gene ProductsRNA SeqRNA StabilityRNA sequencingRNA-Binding ProteinsRNAseqRUNX1RUNX1 geneRegimenRegulationRelapseReportingResolutionRibonucleic AcidRoleSCYB12SDF-1SDF-1ASDF-1BSDF-1alphaSDF1SDF1ASDF1BSTK-1 kinaseSTK1Sdf1 proteinSequence AlterationSignal TransductionSignal Transduction SystemsSignalingStem Cell Tyrosine Kinase 1Stromal Cell-Derived Factor 1Survival RateTLSF-ATLSF-BTPAR1TestingTherapeuticTranscriptTranscriptionTransfer RNATransgenic OrganismsTreatment EfficacyTriplet Codon-Amino Acid AdaptorValidationY-Box-Binding Protein 1YB-1 Y box binding proteinYB-1 binding proteinacute granulocytic leukemiaacute myeloid leukemiaadverse consequenceadverse outcomebiologicbiological signal transductionbisulfite sequencingbisulfite-seqblood cancerblood stem cell regenerationblood stem cell self-renewalcancer microenvironmentcancer of bloodcancer of the bloodchemokine receptorchemoresistantchemotherapy resistancechemotherapy resistantclinical prognosisconventional therapyconventional treatmentdemethylationdevelopmentaldrug resistantepitranscriptomicsfetal liver kinase-2fetal liver kinase-3gain of functiongenome mutationgenomic alterationglobal gene expressionglobal transcription profilehDNA methyltransferase 3ahIRHhematopoietic progenitor cell self-renewalhematopoietic stem cell regenerationhematopoietic stem cell self-renewalhigh riskimprovedin vivoinfancyinfantileinhibitorintervention efficacyknockin miceleukemialeukemia stem/initiating cellsleukemic progenitorleukemic stem cellleukemogenesisloss of functionmRNAmigrationmouse modelmurine modelmutantnew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic targetnew therapy targetnovelnovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic targetnovel therapy targetoverexpressoverexpressionoxidationpathwaypatient derived xenograft modelpatient oriented outcomespharmacologicprogramsregeneration of blood stem cellsresistance to Drugresistant to Drugresolutionsself - renewal in hematopoietic stem cellsself-renewself-renewalsocial rolestromal cell-derived factor-1alphatRNAtherapeutic efficacytherapy efficacytranscriptometranscriptome sequencingtranscriptomic sequencingtransfer Ribonucleic acidstransgenictranslational medicinetumor microenvironmentvalidations
Description preview
PROJECT SUMMARY: Background: Acute myeloid leukemia (AML) is one of the most aggressive types of
hematopoietic malignancies with various genetic alterations. Ten-Eleven Translocation 2 (TET2), an enzyme
involved in DNA demethylation, is deleted or mutated in 15-20% of AML patients. Those patients with TET2
deficiency are poorly responsive to…
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