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Mechanism and therapeutic opportunities of targeting the Tudor domain
Organization BECKMAN RESEARCH INSTITUTE/CITY OF HOPELocation DUARTE, UNITED STATESPosted 1 Dec 2022Deadline 16 Feb 2025 ⚠️
NIHUS FederalResearch GrantFY2025ALL1ALL1 geneAcetylationAchievementAchievement AttainmentAcute Lymphoblastic Leukemia Protein 1Acute leukemiaAffectAnimalsArginineBindingBiochemicalBromodomainCRISPRCRISPR editing screenCRISPR libraryCRISPR screenCRISPR-based libraryCRISPR-based screenCRISPR/Cas systemCRISPR/Cas9 libraryCRISPR/Cas9 screenCXXC7Cancer GenesCancer-Promoting GeneCancersCell BodyCell Communication and SignalingCell LineCell SignalingCellLineCellsClassificationClinicalClustered Regularly Interspaced Short Palindromic RepeatsClustered Regularly Interspaced Short Palindromic Repeats libraryCodeCoding SystemCombined Modality TherapyComplexDNA RearrangementDrosophila Homolog of TrithoraxEC 2.1.1Early-Stage Clinical TrialsElementsEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessFutureGene Action RegulationGene ExpressionGene Expression RegulationGene RearrangementGene RegulationGene Regulation ProcessGenesGeneticGenetic ScreeningGoalsHRXHistone AcetylaseHistone AcetylationHistone DeacetylationHistone H3HistonesHumanInfant LeukemiaIntracellular Communication and SignalingKMT2AL-ArginineL-LysineLeadLeftLysineLysine-Specific Methyltransferase 2AMLL geneMLL rearrangedMLL rearrangementMLL-AF9MLL-rearranged leukemiaMLL/AF9 AMLMLL1MaintenanceMalignant NeoplasmsMalignant TumorMediatingMethylationMethyltransferaseMixed Lineage Leukemia GeneMixed-Lineage Leukemia ProteinModern ManMolecular InteractionMonitorMultimodal TherapyMultimodal TreatmentMultiple lineage leukemia 1Myeloid-Lymphoid Leukemia GeneMyeloid-Lymphoid Leukemia ProteinMyeloid/Lymphoid Leukemia GeneMyeloid/Lymphoid Or Mixed Lineage Leukemia ProteinMyeloid/Lymphoid or Mixed Lineage Leukemia GeneNatureOncogenesOncogenicPDX modelPathway interactionsPatient derived xenograftPatientsPb elementPharmaceutical AgentPharmaceuticalsPharmacologic SubstancePharmacological SubstancePhase 1 Clinical TrialsPhase I Clinical TrialsPositionPositioning AttributePrognosisProteinsProto Oncogene Proteins MLLPublishingReaderRegimenReportingResearchRoleSAGASIRT1SIRT1 geneSPT/ADA/Gcn5 AcetyltransferaseScanningSignal TransductionSignal Transduction SystemsSignalingSirtuin 1Strains Cell LinesSurfaceSurvival RateSystematicsTailTechnologyTherapeuticToxic effectToxicitiesTranscription ActivationTranscriptional ActivationTransforming GenesWorkWorld Health OrganizationZinc Finger Protein HRXbiological signal transductioncancer typechromatin modificationclinical relevanceclinically relevantclustered regularly interspaced short palindromic repeats screencombination therapycombinatorialcombined modality treatmentcombined treatmentcultured cell linedrug discoveryepigeneticallygenetic approachgenetic strategygenome scalegenome-widegenomewideheavy metal Pbheavy metal leadhistone acetyltransferasehistone methylationimprovedin vivoinfant acute leukemiainhibitorinnovateinnovationinnovativeinsightleukemialeukemogenesismalignancymethylasemixed lineage leukemia 1multi-modal therapymulti-modal treatmentmultiomicsmultiple omicsneoplasm/cancernew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeuticsnew therapynew therapy approachesnew treatment approachnew treatment strategynext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeuticsnovel therapynovel therapy approachpanomicspathwaypatient derived xenograft modelpharmaceuticalpharmacologicphase I protocolpre-clinicalpreclinicalprogramsprotein foldingrecruitresponseresponse to therapyresponse to treatmentsocial roletargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic responsetherapy responsetransmethylasetreatment responsetreatment responsiveness
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PROJECT SUMMARY/ABSTRACT
MLL-rearranged (MLL-r) leukemias account for 5-10% of human acute leukemia and is associated with
poor prognosis. The unmet clinical needs and the lack of an effective targeted therapy to the MLL-r
leukemias emphasize the need for novel regimens. Recent cancer epigenetics studies discovered a central
role for the histone…
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