2015
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia
Shojaee S, Caeser R, Buchner M, Park E, Swaminathan S, Hurtz C, Geng H, Chan LN, Klemm L, Hofmann WK, Qiu YH, Zhang N, Coombes KR, Paietta E, Molkentin J, Koeffler HP, Willman CL, Hunger SP, Melnick A, Kornblau SM, Müschen M. Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Cancer Cell 2015, 28: 114-128. PMID: 26073130, PMCID: PMC4565502, DOI: 10.1016/j.ccell.2015.05.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Transformation, NeoplasticDNA-Binding ProteinsDual Specificity Phosphatase 6Host Cell Factor C1HumansIntracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMembrane ProteinsMiceMice, TransgenicMolecular Sequence DataPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProtein Serine-Threonine KinasesSmall Molecule LibrariesTranscription FactorsConceptsAcute lymphoblastic leukemiaLymphoblastic leukemiaPatient-derived preNegative feedback regulationPre-B cell cloneCell deathImmediate cell deathMouse modelSmall molecule inhibitorsTherapeutic targetAcute activationMalignant transformationCell clonesFeedback regulationOncogenic signalingMolecule inhibitorsStrong activationLeukemiaDeathERKPre-B-cell transformationCell transformationActivationOncogenic transformationVast majoritySelf-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia
Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen WY, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH, Müschen M. Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia. Cancer Cell 2015, 27: 409-425. PMID: 25759025, PMCID: PMC4618684, DOI: 10.1016/j.ccell.2015.02.003.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsClinical Trials as TopicDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasePre-B-Cell Leukemia Transcription Factor 1Precursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-6Signal TransductionSrc-Family KinasesSyk KinaseUp-RegulationConceptsDistinct subtypesPre-BCR signalingPatient-derived preVivo treatment studiesTreatment of patientsAcute lymphoblastic leukemiaTyrosine kinase inhibitorsPre-B cell receptor signalingCell receptor signalingLymphoblastic leukemiaClinical trialsTreatment studiesPre-BCR functionReceptor signalingKinase inhibitorsDistinct subsetsBCL6 expressionInduced activationFeedback activationSubtypesTyrosine kinaseBCL6SignalingActivationTranscriptional level
2013
BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint
Swaminathan S, Huang C, Geng H, Chen Z, Harvey R, Kang H, Ng C, Titz B, Hurtz C, Sadiyah MF, Nowak D, Thoennissen GB, Rand V, Graeber TG, Koeffler HP, Carroll WL, Willman CL, Hall AG, Igarashi K, Melnick A, Müschen M. BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. Nature Medicine 2013, 19: 1014-1022. PMID: 23852341, PMCID: PMC3954721, DOI: 10.1038/nm.3247.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic-Leucine Zipper Transcription FactorsCell DeathCell DifferentiationCell SurvivalCell Transformation, NeoplasticDNA-Binding ProteinsGene DeletionGene Expression Regulation, LeukemicGreen Fluorescent ProteinsImmunoglobulin mu-ChainsMiceMolecular Sequence DataPAX5 Transcription FactorPre-B Cell ReceptorsPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycRNA, MessengerSTAT5 Transcription FactorTreatment OutcomeTumor Suppressor Protein p53V(D)J Recombination
2007
Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1–transformed acute lymphoblastic leukemia cells
Feldhahn N, Henke N, Melchior K, Duy C, Soh BN, Klein F, von Levetzow G, Giebel B, Li A, Hofmann WK, Jumaa H, Müschen M. Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1–transformed acute lymphoblastic leukemia cells. Journal Of Experimental Medicine 2007, 204: 1157-1166. PMID: 17485517, PMCID: PMC2118573, DOI: 10.1084/jem.20062662.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBlotting, WesternB-LymphocytesCytidine DeaminaseDNA Mutational AnalysisDNA-Binding ProteinsFlow CytometryFusion Proteins, bcr-ablGene Expression Regulation, NeoplasticGenes, mycHumansImmunoglobulin Variable RegionMolecular Sequence DataMutationOligonucleotide Array Sequence AnalysisOligonucleotidesPhiladelphia ChromosomePrecursor Cell Lymphoblastic Leukemia-LymphomaProtein-Tyrosine KinasesProto-Oncogene Proteins c-bcl-6Reverse Transcriptase Polymerase Chain ReactionRNA InterferenceSequence AlignmentConceptsAcute lymphoblastic leukemiaBCR-ABL1BCR-ABL1 kinaseUnfavorable prognosisActivation-induced cytidine deaminaseAcute lymphoblastic leukemia cellsAID expressionAberrant AID expressionBCR-ABL1 kinase activityIgH V region genesTumor suppressor gene CDKN2BGerminal center B cellsLymphoblastic leukemia cellsB cell precursorsImmunoglobulin heavy chain variable region genesLymphoblastic leukemiaLeukemia subsetsB cellsDNA single-strand breaksPH casesPhiladelphia chromosomeHeavy chain variable region genesAberrant expressionCell precursorsChain variable region genes
2006
SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells
Sprangers M, Feldhahn N, Liedtke S, Jumaa H, Siebert R, Müschen M. SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells. Oncogene 2006, 25: 5180-5186. PMID: 16636677, DOI: 10.1038/sj.onc.1209520.Peer-Reviewed Original ResearchConceptsLymphoblastic leukemiaRecombinase activityRAG1/2 expressionB-cell lineage leukemiaDouble-strand break eventsLymphoma cellsSecondary genetic aberrationsB-cell lymphomaB-cell lymphoma cellsB-lymphoid malignanciesB-cell malignanciesB cell receptorVH gene rearrangementsMalignant progressionLeukemiaFrequent featureGenetic aberrationsGene rearrangementsCells resultsRearrangement activityLineage leukemiaMalignancyVH replacementDeficiencyExpression
2000
Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma
Müschen M, Rajewsky K, Bräuninger A, Baur A, Oudejans J, Roers A, Hansmann M, Küppers R. Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma. Journal Of Experimental Medicine 2000, 191: 387-394. PMID: 10637283, PMCID: PMC2195757, DOI: 10.1084/jem.191.2.387.Peer-Reviewed Original ResearchMeSH KeywordsAdultBase SequenceHodgkin DiseaseHumansLymphoma, T-CellMaleMiddle AgedMolecular Sequence DataReed-Sternberg CellsConceptsTCR beta locusMature B cellsGene rearrangementsCell-associated proteinsLight chain gene rearrangementsClassical Hodgkin's diseaseDJ gene rearrangementsIg gene rearrangementsSingle-cell polymerase chain reactionIgH locusCases of cHDClonal progenyBeta gene rearrangementsT cell receptorT cell moleculesLociGermline configurationCell phenotypeCell moleculesLineage derivationB cellsRS cellsCell receptorImmunoglobulin heavyCell markers