2018
Autonomous Ca2+ Oscillations Reflect Oncogenic BCR-Signaling in Multiple B-Cell Malignancies and Are Essential for Survival and Proliferation
Kume K, Chen L, Lee J, Muschen M. Autonomous Ca2+ Oscillations Reflect Oncogenic BCR-Signaling in Multiple B-Cell Malignancies and Are Essential for Survival and Proliferation. Blood 2018, 132: 1373. DOI: 10.1182/blood-2018-99-117315.Peer-Reviewed Original ResearchAutonomous Ca2B-cell malignanciesBCR signalingProliferation signalsTime of diagnosisExpression levelsINCA-6B-ALLCell deathMantle cell lymphomaMedian expression levelBCR-ABL1Store-operated Ca2Cell lymphomaHigh expression levelsGenetic experimentsT-cell factorMyeloma cellsPatient-derived xenograft modelsMultiple B-cell malignanciesSurvival signalsFunctional BCRSTIM1/2Relapse-free survivalB-cell lymphoma cells
2016
Oncogenic Feedback Activation Between BCL6 and MLL Promotes Malignant Transformation in MLL-RearrangedAcute Lymphoblastic Leukemia
Hurtz C, Chan L, Ballabio E, Willman C, Carroll W, Armstrong S, Ernst P, Melnick A, Milne T, Müschen M. Oncogenic Feedback Activation Between BCL6 and MLL Promotes Malignant Transformation in MLL-RearrangedAcute Lymphoblastic Leukemia. Blood 2016, 128: 907. DOI: 10.1182/blood.v128.22.907.907.Peer-Reviewed Original ResearchFunction of Bcl6Lymphoblastic leukemiaMLL-AF4Expression levelsPhiladelphia chromosome-positive acute lymphoblastic leukemiaBCL6 levelsPharmacological inhibitionDiffuse large B-cell lymphomaLarge B-cell lymphomaChemotherapy drugs vincristineTime of diagnosisWorse clinical outcomesBCL6 expressionHigh expression levelsRelapse-free survivalAcute lymphoblastic leukemiaChronic myeloid leukemiaB-cell lymphomaHigh-risk regimenMLL-ENLTransplant recipient miceB cell precursorsReporter mouse modelWestern blot analysisClinical outcomesFeedback 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 outcomesCD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies
Lee J, Geng H, Chen Z, Klemm L, Cosgun K, Xiao G, Masouleh B, Hurtz C, Parekh S, Kornblau S, Melnick A, Abbas A, Paietta E, Müschen M. CD25 Enables Oncogenic BCR Signaling and Represents a Therapeutic Target in Refractory B Cell Malignancies. Blood 2016, 128: 4088. DOI: 10.1182/blood.v128.22.4088.4088.Peer-Reviewed Original ResearchB-cell malignanciesB-cell tumorsB cell receptorPoor clinical outcomeCell tumorsCell malignanciesClinical outcomesCD25 expressionB-cell leukemiaT cellsClinical cohortCell leukemiaTherapeutic targetB cellsRefractory B-cell malignanciesCell receptorExpression levelsMultiple B-cell malignanciesTumor clonesRegulatory T cellsHigh expression levelsDivergent clinical outcomesBCR signalingHuman B-cell malignanciesB-cell lymphoma cells
2014
PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells
Shojaee S, Cazzaniga V, Schjerven H, Buchner M, Hurtz C, Geng H, Hochhaus A, Cazzaniga G, Melnick A, Kornblau S, Graeber T, Muschen M. PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells. Blood 2014, 124: 262. DOI: 10.1182/blood.v124.21.262.262.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAlleles of PTENDeletion of PTENPI3K-Akt pathwayPI3K-Akt signalingGlucocorticoid resistanceHuman preSmall molecule inhibitorsBCR-ABL1Expression levelsMyeloid lineage leukemiasPatient-derived prePTEN deletionT-cell acute lymphoblastic leukemiaCell acute lymphoblastic leukemiaHigh expression levelsLeukemia cellsTime of diagnosisPoor clinical outcomeCell deathMature B-cell lymphomasPTEN inhibitionHuman cancersLeukemia/lymphomaB-cell lymphoma
2013
Ifitm3 (CD225) Mediates CD19-Dependent Survival and Proliferation During Normal B Cell Development and In Ph+ ALL
Lee J, Geng H, Chen Z, Park E, Klemm L, Bailey C, Muschen M. Ifitm3 (CD225) Mediates CD19-Dependent Survival and Proliferation During Normal B Cell Development and In Ph+ ALL. Blood 2013, 122: 2505. DOI: 10.1182/blood.v122.21.2505.2505.Peer-Reviewed Original ResearchB cell progenitorsC-myc expressionOverall survivalCell cycle arrestCell progenitorsB cellsBCR-ABL1Minimal residual disease statusResidual disease statusSignificant inhibitionTime of diagnosisG0/G1 cell cycle arrestHigh expression levelsPoor overall survivalExpression of CD19Treatment of adriamycinSurface expressionCycle arrestBCR-ABL1 activityG1 cell cycle arrestExpression levelsG0/G1 phaseCellular senescenceLow surface expressionLevels of p53
2012
Targeting BCL6-Mediated Drug-Resistance in High-Risk Childhood ALL
Hurtz C, Ramezani-Rad P, Geng H, Kharabi B, Carroll W, Willman C, Armstrong S, Melnick A, Muschen M. Targeting BCL6-Mediated Drug-Resistance in High-Risk Childhood ALL. Blood 2012, 120: 776. DOI: 10.1182/blood.v120.21.776.776.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaMLL-AF4High expression levelsBCL6 expressionExpression levelsB-cell lineage leukemiaHigh-risk childhood leukemiaMinimal residual disease statusNOD/SCID miceLarge B-cell lymphomaAberrant expressionFunction of Bcl6High-risk childhoodOnset of chemotherapyResidual disease statusTime of diagnosisPoor clinical outcomeProtein levelsBCR-ABL1 kinase activityB-cell lymphomaHigh-risk regimenBone marrow precursor cellsTransplant recipient miceGenetic mouse modelsB cell precursorsSuppressor 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
2010
Dominant-Negative Impact of PAX5/TEL on Downstream Targets of PAX5 and Essential Pre-B Cell Receptor Genes
Iwanski G, Thoennissen N, Nakitandwe J, Lin P, Kawamata N, Nahar R, Ramezani-Rad P, Chen S, Shurtleff S, Nowak D, Ruckert C, Dugas M, Bokemeyer C, Fazio G, Biondi A, Cazzaniga G, Downing J, Müschen M, Koeffler H. Dominant-Negative Impact of PAX5/TEL on Downstream Targets of PAX5 and Essential Pre-B Cell Receptor Genes. Blood 2010, 116: 3231. DOI: 10.1182/blood.v116.21.3231.3231.Peer-Reviewed Original ResearchB cell developmentPre-BCR signalingDominant-negative impactCell developmentTarget genesReporter constructsTyrosine kinasePre-B cell receptorPax5 target genesWild-type PAX5CCAAT/enhancer binding protein alphaBruton's agammaglobulinemia tyrosine kinaseTranscription factor Pax5Downstream target genesGene expression profilesDominant negative roleBCR pathwayGene expression dataLuciferase reporter constructsEndogenous Pax5High expression levelsTranscriptional activationAffymetrix HG-U133Downstream genesExpression of PAX5
2008
The Pre-B Cell Receptor Suppresses Leukemogenesis by Censoring MYC Expression.
Nahar R, Trageser D, Klemm L, Duy C, van Essen P, Kim Y, Heisterkamp N, Martinelli G, Hofmann W, Jack H, Jumaa H, Muschen M. The Pre-B Cell Receptor Suppresses Leukemogenesis by Censoring MYC Expression. Blood 2008, 112: 1918. DOI: 10.1182/blood.v112.11.1918.1918.Peer-Reviewed Original ResearchPre-B cell receptorPre-B cell receptor expressionPre-B cell receptor signalingFunctional pre-B cell receptorEarly pre-B cell stagePre-B cell stageCell receptor signalingSubstantial growth advantageB cell precursorsCell stageE2A-PBX1Receptor signalingCell receptorCell precursorsEarly B cell developmentGrowth advantageComparative gene expressionMYC expressionMLL-AF4Cell receptor expressionB cell developmentMYC mRNA levelsHeavy chain locusHigh expression levelsBCR-ABL1 oncogene