2013
Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy
Hsieh YT, Gang EJ, Geng H, Park E, Huantes S, Chudziak D, Dauber K, Schaefer P, Scharman C, Shimada H, Shojaee S, Klemm L, Parameswaran R, Loh M, Kang ES, Koo HH, Hofmann WK, Andrade J, Crooks GM, Willman CL, Müschen M, Papayannopoulou T, Heisterkamp N, Bönig H, Kim YM. Integrin alpha4 blockade sensitizes drug resistant pre-B acute lymphoblastic leukemia to chemotherapy. Blood 2013, 121: 1814-1818. PMID: 23319569, PMCID: PMC3591800, DOI: 10.1182/blood-2012-01-406272.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedBone MarrowCell AdhesionChildDrug Resistance, NeoplasmFlow CytometryFusion Proteins, bcr-ablHumansIntegrasesIntegrin alpha4MiceMice, Inbred NODMice, KnockoutMice, SCIDNatalizumabNeoplasm, ResidualPrecursor B-Cell Lymphoblastic Leukemia-LymphomaReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerStromal CellsConceptsBone marrowMalignant B-cell precursorsNOD/SCID recipientsAcute lymphoblastic leukemia cellsLeukemia cellsAcute lymphoblastic leukemiaLack of efficacyMinimal residual diseaseLymphoblastic leukemia cellsB cell precursorsModels of leukemiaSCID recipientsPoor outcomeResidual diseaseCurrent therapiesLymphoblastic leukemiaChemotherapyConditional deletionBlockadeIntegrin alpha4LeukemiaGene expression analysisCellsAlpha4Novel strategy
2011
Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia
Park E, Gang EJ, Hsieh YT, Schaefer P, Chae S, Klemm L, Huantes S, Loh M, Conway EM, Kang ES, Koo H, Hofmann WK, Heisterkamp N, Pelus L, Keerthivasan G, Crispino J, Kahn M, Müschen M, Kim YM. Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia. Blood 2011, 118: 2191-2199. PMID: 21715311, PMCID: PMC3162353, DOI: 10.1182/blood-2011-04-351239.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCombined Modality TherapyDrug Resistance, NeoplasmGene ExpressionGene TargetingHumansInhibitor of Apoptosis ProteinsMiceMice, Inbred NODMice, KnockoutNeoplasm, ResidualOligonucleotidesPrecursor Cell Lymphoblastic Leukemia-LymphomaRepressor ProteinsRNA, Small InterferingSurvivinTumor Stem Cell AssayXenograft Model Antitumor AssaysConceptsAcute lymphoblastic leukemiaDrug resistanceLymphoblastic leukemiaDrug-resistant acute lymphoblastic leukemiaDetectable minimal residual diseasePrimary acute lymphoblastic leukemiaNucleic acid antisense oligonucleotideMinimal residual diseaseInhibition of survivinResidual diseaseSurvival advantageXenograft modelSurvivin expressionSurvivin inhibitionLeukemiaSurvivinChemotherapyRelapseAntisense oligonucleotideSurvivin/BIRC5Present studyApoptosis proteinInhibitionCellsPatientsBCL6 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