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 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
2013
Identification Of BCL6 As a Therapeutic Target In MLL-Rearranged ALL
Hurtz C, Geng H, Ballabio E, Xiao G, Ng C, Masouleh B, Willman C, Armstrong S, Milne T, Melnick A, Muschen M. Identification Of BCL6 As a Therapeutic Target In MLL-Rearranged ALL. Blood 2013, 122: 72. DOI: 10.1182/blood.v122.21.72.72.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaFunction of Bcl6White blood countPoor clinical outcomeAcute lymphoblastic leukemiaMinimal residual diseaseClinical outcomesMLL-AF4Clinical trialsBCL6 levelsPositive minimal residual diseasePharmacological inhibitionHigher white blood countExpression levelsLarge B-cell lymphomaAberrant expressionChemotherapy drugs vincristineBCL6 protein levelsTime of diagnosisWorse clinical outcomesBCL6 expressionRelapse-free survivalProtein levelsPediatric clinical trialsB-cell lymphomaThe Plasma Cell Transcription Factor XBP1 is Required To Mitigate The Unfolded Protein Response In Ph+ ALL
Masouleh B, Geng H, Hurtz C, Huang C, Chan L, Swaminathan S, Sun H, Koeffler H, Melnick A, Paietta E, Glimcher L, Muschen M. The Plasma Cell Transcription Factor XBP1 is Required To Mitigate The Unfolded Protein Response In Ph+ ALL. Blood 2013, 122: 836. DOI: 10.1182/blood.v122.21.836.836.Peer-Reviewed Original ResearchRelapse-free survivalX-box binding protein 1White blood cell countPR domain zinc finger protein 1Minimal residual diseaseLeukemia-initiating cellsOverall survivalMultiple myelomaPlasma cellsB cellsClinical relevanceWorse relapse-free survivalUnfolded protein responseXBP1 activationHigh expressionOnset of chemotherapyLeukemia cellsPoor overall survivalBlood cell countInducible CreProtein 1Improved treatment optionsBCR-ABL1 kinase activityTranscription factor X-box binding protein 1Bone marrow B cells
2012
Targeting the UPR-Transcription Factor XBP1 to Overcome Drug-Resistance in Ph+ ALL
Masouleh B, Hurtz C, Geng H, Ramezani-Rad P, Glimcher L, Muschen M. Targeting the UPR-Transcription Factor XBP1 to Overcome Drug-Resistance in Ph+ ALL. Blood 2012, 120: 872. DOI: 10.1182/blood.v120.21.872.872.Peer-Reviewed Original ResearchX-box binding protein 1Relapse-free survivalMultiple myelomaSTF-083010Overall survivalPlasma cellsMinimal residual disease statusPKR-like ER kinaseOnset of chemotherapyLeukemia cellsResidual disease statusPoor overall survivalInducible CreImproved treatment optionsPlasma cell malignancyBone marrow B cell precursorsBone marrow progenitor cellsPresence of IL7ER stressTransplant recipient micePotential clinical relevanceUnfolded protein responseNormal bone marrowB cell precursorsMarrow progenitor cells