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Biology and novel therapy of AML expressing somatic or germline mutant RUNX1
Organization UNIVERSITY OF TX MD ANDERSON CAN CTRLocation HOUSTON, UNITED STATESPosted 1 Dec 2020Deadline 30 Nov 2025 β οΈ
NIHUS FederalResearch GrantFY2025AML1AMLCR1AgeAllogeneic TransplantationApoptosisApoptosis PathwayB cell lymphoma 2B-Cell CLL/Lymphoma 2 GeneB-Cell Chronic Lymphocytic Leukemia Associated OncogeneB-cell Leukemia 1B-cell lymphoma/leukemia-2BCLBCL1 OncogeneBCL2BCL2 geneBackBasal Transcription FactorBasal transcription factor genesBcl-2BindingBiologyBlood Precursor CellBromodomainC-terminalCBFCBFA2CRISPR editing screenCRISPR screenCRISPR-based screenCRISPR/Cas9 screenCancer GenesCancer-Promoting GeneCell BodyCell LineCell modelCellLineCellsCellular modelChromatinComplexCore-Binding FactorCoupledDNA BindingDNA Binding InteractionDNA Polymerase IIDNA Polymerase epsilonDNA boundDNA mutationDNA-Dependent DNA Polymerase IIDependenceDorsumDysmyelopoietic SyndromesEngraftmentEnhancersExhibitsExonsFamilial Platelet DisorderGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGeneralized GrowthGenesGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGerm LinesGerm-Line MutationGrowthGvHDHematopoiesisHematopoietic Cellular Control MechanismsHematopoietic Progenitor CellsHematopoietic stem cellsHereditary MutationHeterozygoteHomologous TransplantationHomologous Wasting DiseaseIn VitroInduction of ApoptosisIntervening SequencesIntronsIsoformsLengthLibrariesMalignantMalignant - descriptorMapsMediatingMessenger RNAMiceMice MammalsMolecular InteractionMurineMusMutationMyelodysplastic DiseaseMyelodysplastic SyndromesMyeloid DiseaseMyeloid MalignancyMyeloid NeoplasmMyeloid TumorMyeloproliferative DisordersMyeloproliferative TumorsMyeloproliferative diseaseNetwork-basedNon-Polyadenylated RNAOncogenesOutcomePDX modelPEBP2A2PEBP2aBPatient derived xenograftPatientsPol IIProgenitor CellsPrognosisProgrammed Cell DeathProtacProtein IsoformsProteinsProteolysis targeting chimericRNARNA ExpressionRNA Gene ProductsRUNX1RUNX1 geneReaderRecurrent diseaseRefractory Anemia with an Excess of BlastsRefractory anaemia with excess blastsRelapsed DiseaseRepressionResidualResidual stateResistanceRibonucleic AcidRiskRunt DiseaseSmoldering LeukemiaSomatic MutationStrains Cell LinesTimeTissue GrowthTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTranscriptional Activation DomainTranscriptional ControlTranscriptional RegulationTransforming Genesagesantagonismantagonistautosomebcl-2 Genesblood cell formationblood cell progenitorblood progenitorblood stem cellblood-forming stem cellced9 homologchemotherapychromatin proteinclustered regularly interspaced short palindromic repeats screencofactorcultured cell lineepigenomegenome mutationgerm-line defectgermline variantglobal gene expressionglobal transcription profilegraft versus host diseasegraft vs host diseasegraft vs. host diseasehematopoietic progenitorhematopoietic stem progenitor cellhemopoietic progenitorhemopoietic stem cellheterozygosityhomoharringtonineimprovedin vivoinhibitorknock-downknockdownloss of function mutationmRNAmutantmyelodysplasiamyeloproliferative neoplasmnew drug targetnew drug treatmentsnew druggable targetnew drugsnew pharmacological therapeuticnew pharmacotherapy targetnew therapeutic targetnew therapeuticsnew therapynew therapy targetnext generation therapeuticsnovelnovel drug targetnovel drug treatmentsnovel druggable targetnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel pharmacotherapy targetnovel therapeutic targetnovel therapeuticsnovel therapynovel therapy targetontogenypatient derived xenograft modelpre-clinicalpre-clinical efficacypreclinicalpreclinical efficacyproteolysis targeting chimaeraproteolysis targeting chimerarecruitresistantshRNAshort hairpin RNAsmall hairpin RNAsomatic variantstem cellstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttranscription factortranscriptome
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Project Summary:
RUNX1 is the DNA-binding subunit of the core binding factor (CBF) complex and a master-regulator
transcription factor, which is involved in normal and malignant hematopoiesis. Somatic, heterozygous RUNX1
mutations commonly occur in Myelodysplastic Syndrome (MDS) (10%), as well as in secondary (s) or de novo
AML (~10%). Germlineβ¦
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