2019
Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation
Cosgun K, Deb G, Yang X, Xiao G, Sadras T, Lee J, Chan L, Kume K, Yang L, Geng H, Chan J, Song J, Jumaa H, Polson A, Clevers H, Müschen M. Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation. Blood 2019, 134: 748. DOI: 10.1182/blood-2019-127263.Peer-Reviewed Original ResearchB-cell lineage acute lymphoblastic leukemiaWnt/β-catenin signalingΒ-catenin signalingNuclear β-cateninAntibody-drug conjugatesB cell developmentB cell survivalΒ-cateninB lymphopoiesisFunction of LGR5Median mRNA levelsTime of diagnosisPoor clinical outcomeRole of LGR5Acute lymphoblastic leukemiaB-cell lymphomaLeukemia initiating cellsWnt/β-cateninHigh surface expressionMalignant B-cell transformationCell linesB cell precursorsTypes of cancerHuman colon cancer cell linesB-cell lineage
2015
Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia
Buchner M, Park E, Geng H, Klemm L, Flach J, Passegué E, Schjerven H, Melnick A, Paietta E, Kopanja D, Raychaudhuri P, Müschen M. Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia. Nature Communications 2015, 6: 6471. PMID: 25753524, PMCID: PMC4366523, DOI: 10.1038/ncomms7471.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntineoplastic AgentsB-LymphocytesCell ProliferationCell SurvivalChildClinical Trials as TopicCyclin-Dependent Kinase Inhibitor p16Drug Resistance, NeoplasmForkhead Box Protein M1Forkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, LeukemicHumansMicePeptidesPrecursor Cell Lymphoblastic Leukemia-LymphomaSignal TransductionSurvival AnalysisThiostreptonXenograft Model Antitumor AssaysConceptsAcute lymphoblastic leukemiaLymphoblastic leukemiaTherapeutic targetB-cell lineage acute lymphoblastic leukemiaFOXM1 levelsAggressive clinical coursePre-B cell receptor checkpointNovel therapeutic targetB cell populationsNormal B cell populationsClinical coursePoor outcomeCure rateNormal B cell developmentFOXM1 inhibitionB cell developmentDrug resistanceFoxm1 deletionFOXM1Colony formationPatientsLeukemiaCell survivalPrognosisTranscriptional inactivation
2009
Activation-Induced Cytidine Deaminase Accelerates Clonal Evolution of BCR-ABL1-Driven B Cell Lineage Acute Lymphoblastic Leukemia.
Gruber T, Chang M, Sposto R, Müschen M. Activation-Induced Cytidine Deaminase Accelerates Clonal Evolution of BCR-ABL1-Driven B Cell Lineage Acute Lymphoblastic Leukemia. Blood 2009, 114: 181. DOI: 10.1182/blood.v114.22.181.181.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAberrant AID expressionBCR-ABL1Lymphoblastic leukemiaB cellsBCR-ABL1 kinase domain mutationsB-cell lineage acute lymphoblastic leukemiaClonal evolutionTumor suppressor geneAberrant somatic hypermutationAID expressionB-cell lymphomaKinase domain mutationsGerminal center B cellsBone marrow cellsSuppressor geneBCR-ABL1 kinaseGC B cellsHazard ratioMedian survivalGenetic instabilityImatinib treatmentSomatic hypermutationB-cell lymphomagenesisCell lymphomaPre–B cell receptor–mediated cell cycle arrest in Philadelphia chromosome–positive acute lymphoblastic leukemia requires IKAROS function
Trageser D, Iacobucci I, Nahar R, Duy C, von Levetzow G, Klemm L, Park E, Schuh W, Gruber T, Herzog S, Kim YM, Hofmann WK, Li A, Storlazzi CT, Jäck HM, Groffen J, Martinelli G, Heisterkamp N, Jumaa H, Müschen M. Pre–B cell receptor–mediated cell cycle arrest in Philadelphia chromosome–positive acute lymphoblastic leukemia requires IKAROS function. Journal Of Experimental Medicine 2009, 206: 1739-1753. PMID: 19620627, PMCID: PMC2722172, DOI: 10.1084/jem.20090004.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAnimalsCell CycleCell Transformation, NeoplasticDown-RegulationGene DeletionGenes, ablHumansIkaros Transcription FactorLeukemia, Prolymphocytic, B-CellMiceMice, KnockoutMice, TransgenicPhiladelphia ChromosomePre-B Cell ReceptorsSignal TransductionConceptsAcute lymphoblastic leukemiaCell cycle arrestPre-B cell receptorCell receptorLymphoblastic leukemiaPre-B cell receptor functionPhiladelphia chromosome-positive acute lymphoblastic leukemiaB-cell lineage acute lymphoblastic leukemiaCycle arrestUnfavorable clinical outcomeBCR-ABL1 tyrosine kinaseB cell precursorsCase of adultsBCR-ABL1 kinaseTumor suppressionClinical outcomesReceptor functionCell precursorsCell receptor functionIkaros functionCell cycle exitDownstream moleculesReceptorsLeukemiaSubtypes
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