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
2011
BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition
Duy C, Hurtz C, Shojaee S, Cerchietti L, Geng H, Swaminathan S, Klemm L, Kweon SM, Nahar R, Braig M, Park E, Kim YM, Hofmann WK, Herzog S, Jumaa H, Koeffler HP, Yu JJ, Heisterkamp N, Graeber TG, Wu H, Ye BH, Melnick A, Müschen M. BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition. Nature 2011, 473: 384-388. PMID: 21593872, PMCID: PMC3597744, DOI: 10.1038/nature09883.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 1AnimalsCell SurvivalDNA-Binding ProteinsDrug Resistance, NeoplasmFusion Proteins, bcr-ablGene Expression Regulation, NeoplasticHumansMiceMice, Inbred NODMice, SCIDPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-6Transcription, GeneticTumor Suppressor Protein p53ConceptsTyrosine kinase inhibitorsAcute lymphoblastic leukemia cellsBCR-ABL1 mutationsLymphoblastic leukemia cellsDrug resistanceLeukemia cellsLeukemia-initiating cellsXenograft modelBCR-ABL1Anticancer responseTargeted inhibitionDual inhibitionKinase inhibitorsOncogene withdrawalCancer therapyBCL6Kinase inhibitionLeukemiaInhibitionCellsTherapyMutationsUpregulation
2009
The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug Resistance in Chronic Myeloid Leukemia
Klemm L, Duy C, Iacobucci I, Kuchen S, von Levetzow G, Feldhahn N, Henke N, Li Z, Hoffmann TK, Kim YM, Hofmann WK, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber MR, Casellas R, Müschen M. The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug Resistance in Chronic Myeloid Leukemia. Cancer Cell 2009, 16: 232-245. PMID: 19732723, PMCID: PMC2931825, DOI: 10.1016/j.ccr.2009.07.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBlast CrisisB-LymphocytesCell Line, TumorCytidine DeaminaseDrug Resistance, NeoplasmFusion Proteins, bcr-ablGreen Fluorescent ProteinsHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLuciferases, RenillaMiceMice, Inbred BALB CMice, KnockoutMice, SCIDMice, TransgenicMutationPiperazinesPyrimidinesXenograft Model Antitumor AssaysConceptsLymphoid blast crisisChronic myeloid leukemiaB-lymphoid blast crisisBCR-ABL1 mutationsDrug resistanceMyeloid leukemiaBlast crisisCML cellsMechanisms of progressionImatinib resistanceClinical significanceBCR-ABL1Causative roleDNA repair genesLeukemia cellsRepair genesLeukemiaTumor suppressorAID expressionOverall genetic instabilityProgressionCellsGenetic instabilityImatinibMutations