2020
Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia
Gang EJ, Kim HN, Hsieh YT, Ruan Y, Ogana HA, Lee S, Pham J, Geng H, Park E, Klemm L, Willman CL, Carroll WL, Mittelman SD, Orgel E, Oberley MJ, Parekh C, Abdel-Azim H, Bhojwani D, Wayne AS, De Arcangelis A, Georges-Labouesse E, Wayner E, Bonig H, Minasyan A, ten Hoeve J, Graeber TG, Müschen M, Heisterkamp N, Kim YM. Integrin α6 mediates the drug resistance of acute lymphoblastic B-cell leukemia. Blood 2020, 136: 210-223. PMID: 32219444, PMCID: PMC7357190, DOI: 10.1182/blood.2019001417.Peer-Reviewed Original ResearchConceptsAcute lymphoblastic leukemiaDrug resistanceTyrosine kinase inhibitor treatmentIntegrin α6Minimal residual diseaseProteomic analysisAcute lymphoblastic B-cell leukemiaAdhesion-mediated drug resistanceKinase inhibitor treatmentNovel therapeutic targetConditional knockout modelCentral nervous systemSrc signalingB-cell leukemiaPhosphorylated LynCell adhesionVivo deletionKnockout modelsResidual diseaseLymphoblastic leukemiaKinase inhibitionTherapeutic targetNervous systemB cellsBCR-ABL1
2015
Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia
Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA, Müschen M. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature 2015, 521: 357-361. PMID: 25799995, PMCID: PMC4441554, DOI: 10.1038/nature14231.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsAntigens, CDB-LymphocytesCell DeathCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDrug Resistance, NeoplasmEnzyme ActivationFemaleFusion Proteins, bcr-ablGene DeletionHumansInositol Polyphosphate 5-PhosphatasesIntracellular Signaling Peptides and ProteinsMiceMice, Inbred NODMice, SCIDPhosphatidylinositol-3,4,5-Trisphosphate 5-PhosphatasesPhosphoric Monoester HydrolasesPlatelet Endothelial Cell Adhesion Molecule-1Precursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProtein Tyrosine Phosphatase, Non-Receptor Type 6Protein-Tyrosine KinasesReceptors, Antigen, B-CellReceptors, ImmunologicSignal TransductionSyk KinaseTyrosineXenograft Model Antitumor Assays
2009
Pre–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