2019
Ifitm3 Is Essential for PI(3,4,5)P3-Dependent B-Cell Activation and Leukemogenesis
Lee J, Xiao G, Cosgun K, Geng H, Ma N, Chan L, Kume K, Nix M, Chen Z, Chen C, Chen J, Khairnar V, Wiita A, Thomas-Tikhonenko A, Farzan M, Diamond M, Jung J, Vaidehi N, Müschen M. Ifitm3 Is Essential for PI(3,4,5)P3-Dependent B-Cell Activation and Leukemogenesis. Blood 2019, 134: 2782. DOI: 10.1182/blood-2019-127615.Peer-Reviewed Original ResearchPoor clinical outcomeB cellsBCR-ABL1Clinical outcomesPI3KAntigen-specific humoral immune responsesAntigen-specific B cell responsesAntiviral effector functionsTime of diagnosisMRNA levelsB cell responsesHumoral immune responseSurface expressionB cell populationsB-cell malignanciesB-cell receptor signalingDependent B cell activationTransplant recipient miceMalignant B-cell transformationB cell activationB cell precursorsColony formation capacityAdvisory CommitteeSrc kinaseB-cell transformation
2018
IFITM3-Mediated Regulation of Cell Membrane Dynamics Is Essential for Malignant B-Cell Transformation
Lee J, Geng H, Dinson D, Xiao G, Cosgun K, Chan L, Chen Z, Farzan M, Jung J, Wiita A, Muschen M. IFITM3-Mediated Regulation of Cell Membrane Dynamics Is Essential for Malignant B-Cell Transformation. Blood 2018, 132: 552. DOI: 10.1182/blood-2018-99-117472.Peer-Reviewed Original ResearchB cell receptorLipid raftsOncogenic tyrosine kinasesTyrosine kinasePlasma membraneCentral regulatorNormal B-cell receptorType II transmembrane topologyPI3KMalignant B-cell transformationIntracellular N terminusHomotypic cellular aggregationCell membraneCo-receptor CD19Assembly of membraneMRNA levelsLipid raft formationCell membrane dynamicsPotent tumor suppressorDifferent cell typesCholesterol accumulationCell cycle arrestCell receptorEndocytic motifTransmembrane topology
2017
PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases
Xiao G, Hong C, Geng H, Muschen M. PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases. Blood 2017, 130: 882. DOI: 10.1182/blood.v130.suppl_1.882.882.Peer-Reviewed Original ResearchPatient-derived preB-cell lineageParaoxonase 2BCR-ABL1PON2 expressionB cell developmentB-lineageExpression levelsAdult clinical trialsPON2-deficient miceTime of diagnosisPoor clinical outcomeMRNA levelsBone marrow B cell precursorsSpecific treatment requirementsLactone metabolitesMultiple fetal tissuesG0/G1 phaseB cell precursorsNormal B cellsCell lineagesNormal hematopoietic cellsCell developmentPON2 deficiencyQuantitative RT-PCR
2016
Feedback Regulation of STAT5 Is Critical to Balance MYC and BCL6-Dependent Transcriptional Programs That Regulate Cell Size and Glucose Metabolism
Chen Z, Geng H, Klemm L, Chan L, Daniel B, Alexander W, Willman C, Müschen M. Feedback Regulation of STAT5 Is Critical to Balance MYC and BCL6-Dependent Transcriptional Programs That Regulate Cell Size and Glucose Metabolism. Blood 2016, 128: 4069. DOI: 10.1182/blood.v128.22.4069.4069.Peer-Reviewed Original ResearchBCR-ABL1Survival rateMedian expressionAdult B-lineageFree survival rateOverall survival rateWorse clinical outcomesGroup of patientsHigh expression levelsLeukemia cellsMRNA levelsNOD-SCID miceMYC expressionTyrosine kinase inhibitorsBCR-ABL1 tyrosine kinaseExpression levelsKinase inhibitory regionMedical Research CouncilAdvisory CommitteeInhibition of mTORGlucose consumptionCOG trialsLeukemia regressionTyrosine kinaseClinical outcomes
2015
IFITM3 (CD225) Links the B Cell Antigen CD19 to PI3K-AKT Signaling in Human ALL Cells
Lee J, Geng H, Chen Z, Eugene P, Klemm L, Bailey C, Muschen M. IFITM3 (CD225) Links the B Cell Antigen CD19 to PI3K-AKT Signaling in Human ALL Cells. Blood 2015, 126: 1325. DOI: 10.1182/blood.v126.23.1325.1325.Peer-Reviewed Original ResearchTime of diagnosisPI3K-Akt signalingPI3K-AktHuman preSurface expressionAgonistic antibodiesB-cell antigen CD19Patient-derived preRelapse-free survivalMRNA levelsChimeric antigen receptorMedian expression levelPI3K p110δSurface receptorsColony formation capacityMRD statusInduction chemotherapyImmunotherapy approachesAntigen CD19Cell cycle arrestCell receptor complexClinical trialsCD19 expressionHigh riskB cell progenitors
2014
IFITM3 (CD225) Regulates CD19 Surface Expression and CD19-Mediated Activation of PI3K Signaling in Pre-B Acute Lymphoblastic Leukemia Cells
Lee J, Geng H, Chen Z, Park E, Park A, Klemm L, Bailey C, Muschen M. IFITM3 (CD225) Regulates CD19 Surface Expression and CD19-Mediated Activation of PI3K Signaling in Pre-B Acute Lymphoblastic Leukemia Cells. Blood 2014, 124: 1070. DOI: 10.1182/blood.v124.21.1070.1070.Peer-Reviewed Original ResearchCD19-specific chimeric antigen receptorTime of diagnosisB cell progenitorsPI3K-AktSurface expressionCell cycle arrestC-myc expressionCD19 expressionCell progenitorsB cellsHuman preAcute lymphoblastic leukemia cellsLow-dose AdriamycinPatient-derived preSignificant inhibitionRelapse-free survivalG0/G1 cell cycle arrestMRNA levelsChimeric antigen receptorExpression of CD19Cycle arrestBCR-ABL1 activityG1 cell cycle arrestLymphoblastic leukemia cellsG0/G1 phase
2012
SOX4 enables Oncogenic Survival Signals in Acute Lymphoblastic Leukemia
Ramezani-Rad P, Geng H, Chan L, Hurtz C, Jumaa H, Melnick A, Paietta E, Carroll W, Willman C, Lefebvre V, Muschen M. SOX4 enables Oncogenic Survival Signals in Acute Lymphoblastic Leukemia. Blood 2012, 120: 863. DOI: 10.1182/blood.v120.21.863.863.Peer-Reviewed Original ResearchARF/p53PI3K/AktTranscription factorsPoor clinical outcomeNegative regulationBCR-ABL1B cell precursorsPre-B cell transitionClinical outcomesDe-phosphorylation eventsCpG methylation analysisMRNA levelsPre-B cell receptor checkpointMyeloid leukemiaP110 catalytic subunitCytokine receptor signalingB cell developmentB-cell lineage leukemiaSOX4 transcription factorTyrosine kinase inhibitor treatmentPI3K/Akt pathwayCell precursorsT cell developmentCritical upstream regulatorPutative DNABACH2 Is Required for Pre-B Cell Receptor Checkpoint Control and p53-Dependent Tumor Surveillance
Swaminathan S, Kang H, Harvey R, Huang C, Buchner M, Chen Z, Geng H, Hall A, Igarashi K, Carroll W, Willman C, Melnick A, Muschen M. BACH2 Is Required for Pre-B Cell Receptor Checkpoint Control and p53-Dependent Tumor Surveillance. Blood 2012, 120: 1300. DOI: 10.1182/blood.v120.21.1300.1300.Peer-Reviewed Original ResearchFavorable clinical outcomeTyrosine kinase inhibitorsPre-B cell cloneOncogene-induced senescenceClinical outcomesLeukemia cellsB cellsBCR-ABL1Multivariate analysisCell clonesAcute lymphoblastic leukemia cellsTime of diagnosisMRNA levelsTumor suppressor CDKN2AGerminal center B cellsLymphoblastic leukemia cellsEvidence of MRDNormal human bone marrowCases of childhoodSigns of diseaseRelapse of childhoodBACH2 locusImmunoglobulin heavy chain geneQuantitative RT-PCRMYC resultsITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL
Chen Z, Geng H, Buchner M, Klemm L, Hemati K, Shojaee S, Tak M, Coligan J, Carroll W, Willman C, Muschen M. ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL. Blood 2012, 120: 291. DOI: 10.1182/blood.v120.21.291.291.Peer-Reviewed Original ResearchBCR-ABL1Leukemia cellsInhibitory receptorsLeukemia cell deathTherapeutic targetSurvival rateCellular senescenceAcute lymphoblastic leukemia cellsFree survival rateOverall survival rateG0/G1 cell cycle arrestMRNA levelsAdditional therapeutic targetsNOD-SCID miceNormal bone marrow samplesBone marrow samplesCycle arrestHalf of casesG1cell cycle arrestLymphoblastic leukemia cellsG1 cell cycle arrestCell deathColony forming assaysCOG trialsLeukemia regressionSuppressor of Cytokine Signaling (SOCS) Molecules Are Critical to Balance Oncogenic Signaling Strength in Ph+ ALL.
Chen Z, Geng H, Klemm L, Buchner M, Hemati K, Shojaee S, Alexander W, Carroll W, Willman C, Muschen M. Suppressor of Cytokine Signaling (SOCS) Molecules Are Critical to Balance Oncogenic Signaling Strength in Ph+ ALL. Blood 2012, 120: 2563. DOI: 10.1182/blood.v120.21.2563.2563.Peer-Reviewed Original ResearchBCR-ABL1Leukemia cellsTherapeutic targetSurvival rateP-STAT5Acute lymphoblastic leukemia cellsFree survival rateOverall survival rateHigh expression levelsG0/G1 cell cycle arrestRole of SOCS2Course of diseaseMRNA levelsAdditional therapeutic targetsNOD-SCID miceInducible deletionG1 cell cycle arrestLymphoblastic leukemia cellsExpression levelsCellular senescenceCOG trialsLeukemia regressionExpression of SOCS2Poor outcomeJAK/STAT pathway
2011
BACH2 Mediates Early B Cell Differentiation and Oncogene-Induced Senescence in Acute Lymphoblastic Leukemia
Swaminathan S, Huang C, Titz B, Buchner M, Geng H, Graeber T, Willman C, Igarashi K, Melnick A, Muschen M. BACH2 Mediates Early B Cell Differentiation and Oncogene-Induced Senescence in Acute Lymphoblastic Leukemia. Blood 2011, 118: 562. DOI: 10.1182/blood.v118.21.562.562.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsRelapse of childhoodBCR-ABL1B cell differentiationDay 29Leukemia cellsB cellsMRNA levelsOverexpression of MYCEarly B cell differentiationAcute lymphoblastic leukemia cellsAcute lymphoblastic leukemiaTumor suppressor CDKN2AGerminal center B cellsLymphoblastic leukemia cellsEvidence of MRDNormal human bone marrowSigns of diseaseCommon gene expression signatureFraction of casesPositive MRDQuantitative RT-PCRRole of Bach2Gene expression signaturesImatinib treatment
1999
CD95 ligand expression in dedifferentiated breast cancer
Müschen M, Moers C, Warskulat U, Niederacher D, Betz B, Even J, Lim A, Josien R, Beckmann M, Häussinger D. CD95 ligand expression in dedifferentiated breast cancer. The Journal Of Pathology 1999, 189: 378-386. PMID: 10547600, DOI: 10.1002/(sici)1096-9896(199911)189:3<378::aid-path439>3.0.co;2-d.Peer-Reviewed Original ResearchConceptsReverse transcriptase-polymerase chain reactionBreast cancerCD95 ligand expressionMRNA levelsLigand expressionGrade III breast cancerMammary tissueCD95L mRNA levelsTumor-infiltrating lymphocytesCD95 ligandHigh-grade carcinomaQuantitative reverse transcriptase-polymerase chain reactionBenign mammary tissuesTissue sectionsBreast cancer tissuesNon-malignant mammary tissuesTranscriptase-polymerase chain reactionBreast cancer tissue sectionsBreast cancer sectionsCancer tissue sectionsGrade IGrade IIHistopathological gradingReceptor expressionCancer tissuesRegulation 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
1998
Regulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells
Müschen M, Warskulat U, Douillard P, Gilbert E, Häussinger D. Regulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells. Hepatology 1998, 27: 200-208. PMID: 9425938, DOI: 10.1002/hep.510270131.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsNumber of KCsCD95L mRNA levelsKupffer cellsParenchymal cellsMRNA levelsNonparenchymal rat liver cellsNonparenchymal cellsCD95L expressionEffects of lipopolysaccharideMeans of immunocytochemistryLiver Kupffer cellsAddition of supernatantsPresence of lipopolysaccharideLiver cell populationsRat liver Kupffer cellsMessenger RNA levelsCD95 receptorLPS treatmentRat liver cellsThymic lymphocytesCD95 expressionLigand expressionLPS additionPrimary hepatocyte cultures