2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCells
2018
Autoimmunity checkpoints as therapeutic targets in B cell malignancies
Müschen M. Autoimmunity checkpoints as therapeutic targets in B cell malignancies. Nature Reviews Cancer 2018, 18: 103-116. PMID: 29302068, DOI: 10.1038/nrc.2017.111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAutoimmunityB-LymphocytesHumansLymphoma, B-CellPrecursor Cell Lymphoblastic Leukemia-LymphomaReceptors, Antigen, B-Cell
2017
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Takao S, Chien W, Madan V, Lin D, Ding L, Sun Q, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang Y, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler H. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia 2017, 32: 616-625. PMID: 28904384, DOI: 10.1038/leu.2017.281.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAminopyridinesAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalCytokinesDisease Models, AnimalFemaleHumansMaleMiceNADNicotinamide PhosphoribosyltransferaseP21-Activated KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSignal TransductionXenograft Model Antitumor AssaysConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaP21-activated kinase 4Nicotinamide phosphoribosyltransferaseLymphoblastic leukemiaNAMPT inhibitionPatient-derived xenograft murine modelsPrognosis of patientsNicotinamide adenine dinucleotideNovel therapeutic strategiesNicotinic acid supplementationNovel dual inhibitorXenograft murine modelCell growth inhibitionAcid supplementationMurine modelTherapeutic strategiesRate-limiting enzymeCytogenetic abnormalitiesVivo efficacyPatientsNAMPT inhibitorsInhibitory effectDual inhibitorKinase 4
2016
Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation
McCracken A, McMonigle R, Tessier J, Fransson R, Perryman M, Chen B, Keebaugh A, Selwan E, Barr S, Kim S, Roy S, Liu G, Fallegger D, Sernissi L, Brandt C, Moitessier N, Snider A, Clare S, Müschen M, Huwiler A, Kleinman M, Hanessian S, Edinger A. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia 2016, 31: 669-677. PMID: 27573555, PMCID: PMC5332311, DOI: 10.1038/leu.2016.244.Peer-Reviewed Original ResearchConceptsS1P receptor activationAnti-leukemic actionProtein phosphatase 2APro-apoptotic targetsPhosphatase 2ASphingosine kinase 2Efficient phosphorylationGenetic approachesReceptor activationKinase 2Nutrient accessChemical biologyPhosphorylationTight inverse correlationDistinct mechanismsS1P receptorsAnti-leukemic activityNovel therapeutic approachesLeukemia progressionReceptor activityMRNA expressionAnti-leukemic agentsActivationEnhanced potencyBiology
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 majorityIdentification 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
2005
BCR–ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells
Klein F, Feldhahn N, Herzog S, Sprangers M, Mooster J, Jumaa H, Müschen M. BCR–ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells. Oncogene 2005, 25: 1118-1124. PMID: 16205638, DOI: 10.1038/sj.onc.1209133.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAntineoplastic AgentsBenzamidesCell Line, TumorCell LineageCell NucleusFusion Proteins, bcr-ablGene Expression ProfilingGene SilencingHumansIkaros Transcription FactorImatinib MesylateMicePiperazinesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrimidinesConceptsLymphoid lineage commitmentLineage commitmentGenome-wide gene expression profilesAberrant splicingLymphoblastic leukemia cellsLeukemia cellsAberrant expressionGene expression profilesNormal B-cell subsetsCell linesPrecursor cell lineLineage identityLineage infidelityTranscription factorsRNA interferenceExpression profilesInducible expressionUndifferentiated phenotypeSplice variantsDefective expressionBCR-ABL1SplicingIk6ExpressionCells
1999
Regulation of CD95 (APO‐1/ FAS) ligand and receptor expression in squamous‐cell carcinoma by interferon‐γ and cisplatin
Moers C, Warskulat U, Müschen M, Even J, Niederacher D, Josien R, Koldovsky U, Beckmann M, Häussinger D. Regulation of CD95 (APO‐1/ FAS) ligand and receptor expression in squamous‐cell carcinoma by interferon‐γ and cisplatin. International Journal Of Cancer 1999, 80: 564-572. PMID: 9935158, DOI: 10.1002/(sici)1097-0215(19990209)80:4<564::aid-ijc14>3.0.co;2-x.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaExpression of CD95LPrimary cell linesPrimary squamous cell carcinomaStroma cellsCD95L expressionAddition of CDDPCD95L mRNA levelsTumor-associated immunosuppressionHuman primary cell linesMRNA levelsEffect of cisplatinCell linesCD95 ligand expressionInvasive tumor tissuesAutologous lymphocytesCell carcinomaReceptor expressionSCC cellsSoluble receptorLigand expressionTumor tissueTumor samplesReceptor isoformsInvasion factors