2021
Leveraging Pathway-Interference to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia
Chan L, Murakami M, Hurtz C, Kume K, Lee J, Cosgun K, Geng H, Izraeli S, Weinstock D, Müschen M. Leveraging Pathway-Interference to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia. Blood 2021, 138: 616. DOI: 10.1182/blood-2021-149773.Peer-Reviewed Original ResearchB-ALLFl/flCancer typesOncogenic driversOncogenic pathwaysPharmacological reactivationPrincipal oncogenic driverMalignant transformationSpeakers bureauAcute lymphoblastic leukemiaGenetic lesionsERK pathwayTGFβ-Smad pathwaySignaling pathwaysMulti-step carcinogenesisERK agonistERK pathway activationOverall survivalNSG miceColorectal cancerInvasive cancerLymphoblastic leukemiaPreclinical studiesPathway interactionsFatal leukemiaBeta-Catenin Forms Repressive Complexes with Ikzf1 and Ikzf3 to Orchestrate Tumor-Suppression in B-Cell Malignancies
Cosgun K, Robinson M, Chan L, Hur M, Leveille E, Song J, Chan W, Müschen M. Beta-Catenin Forms Repressive Complexes with Ikzf1 and Ikzf3 to Orchestrate Tumor-Suppression in B-Cell Malignancies. Blood 2021, 138: 29. DOI: 10.1182/blood-2021-148597.Peer-Reviewed Original ResearchB-cell malignanciesΒ-catenin activationΒ-cateninOncogenic Wnt/β-catenin signalingMalignant B-lymphoid cellsGenetic deletionRefractory B-ALLTranscriptional repressionB-cell lymphomaTumor suppressionWnt/β-catenin signalingΒ-catenin/TCF complexMature B-cell malignanciesB-lymphoid cellsCancer cell linesΒ-catenin signalingClonal fitnessOverall survivalLeukemia burdenNSG miceB-ALLCell cycle arrestNuclear β-cateninPan-cancer analysisFrequent lesions
2018
Lgr5 Enables Positive B-Cell Selection and Tumor-Initiation in B-Cell Malignancies
Cosgun K, Deb G, Yang X, Xiao G, Sadras T, Auer F, Lee J, Abarientos A, Mangolini M, Aghajanirefah A, Geng H, Jumaa H, Polson A, Clevers H, Muschen M. Lgr5 Enables Positive B-Cell Selection and Tumor-Initiation in B-Cell Malignancies. Blood 2018, 132: 547. DOI: 10.1182/blood-2018-99-116956.Peer-Reviewed Original ResearchB-cell malignanciesB-cell lineageAntibody-drug conjugatesLeukemia-initiating cellsTransplant recipientsB-ALLSurface expressionCancer stem cell markersWorse overall survivalMature B cell poolPoor clinical outcomeSingle-agent treatmentΒ-cateninB cell poolB cell selectionStem cell markersΒ-catenin activationΒ-catenin target genesLGR5 overexpressionLIC frequencyOverall survivalLeukemia burdenClinical outcomesEnvironmental antigensRecipient mice
2016
BCL6 Is Critical to Overcome Oncogene-Induced Senescence in RAS-Mediated B Cell Transformation
Chan L, Hurtz C, Xiao G, Shojaee S, Caeser R, Geng H, Melnick A, Müschen M. BCL6 Is Critical to Overcome Oncogene-Induced Senescence in RAS-Mediated B Cell Transformation. Blood 2016, 128: 438. DOI: 10.1182/blood.v128.22.438.438.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaRAS-ERK signalingBCL6 expressionRole of BCL6Recipient micePhiladelphia chromosome-positive acute lymphoblastic leukemiaSTAT5 activityRAS-ERKLarge B-cell lymphomaAbsence of Bcl6Acute lymphoblastic leukemiaNovel mouse modelProto-oncogene Bcl6B-cell lymphomaNovel therapeutic avenuesTransplant recipient miceNovel mechanismMouse embryonic fibroblastsOncogene-Induced SenescenceP53-dependent senescenceB-cell transformationInitial remissionLeukemia relapseOverall survivalImatinib treatment
2015
Expression of B and T Lymphocyte Attenuator (BTLA) Correlates with CNS Metastasis and Adverse Prognosis in Activated B-Cell Lymphoma and Acute Lymphoblastic Leukemia
Geng H, Chen Z, Anderson S, Fraser E, Lu M, Lingjing C, Collins C, Markus M, Rubenstein J. Expression of B and T Lymphocyte Attenuator (BTLA) Correlates with CNS Metastasis and Adverse Prognosis in Activated B-Cell Lymphoma and Acute Lymphoblastic Leukemia. Blood 2015, 126: 3900. DOI: 10.1182/blood.v126.23.3900.3900.Peer-Reviewed Original ResearchPatient-derived cell linesLarge B-cell lymphomaB-cell lymphomaShorter overall survivalAcute lymphoblastic leukemiaHigh BTLA expressionBTLA expressionOverall survivalHigh-resolution array-based comparative genomic hybridizationMurine modelRecurrent copy number gainsDNA copy number aberrationsArray-based comparative genomic hybridizationCell linesCNS metastasisLymphoblastic leukemiaCopy number gainsB cell receptorComparative genomic hybridizationCopy number aberrationsPrimary central nervous system lymphomaGenomic changesCentral nervous system lymphomaTranscript levelsAggressive B-cell lymphomas
2013
The 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 cellsIfitm3 (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 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
2009
The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia.
Klemm L, Duy C, Iacobucci I, von Levetzow G, Feldhahn N, Kim Y, Hofmann W, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber M, Casellas R, Müschen M. The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia. Blood 2009, 114: 3274. DOI: 10.1182/blood.v114.22.3274.3274.Peer-Reviewed Original ResearchBCR-ABL1 mutationsChronic myeloid leukemiaLymphoid blast crisisB-lymphoid blast crisisBCR-ABL1 kinase domainImatinib resistanceCML cellsBCR-ABL1Gene copy number alterationsDrug resistanceLeukemia cellsOverall survivalMyeloid leukemiaBlast crisisFive-year overall survivalCopy number alterationsNOD/SCID miceMedian overall survivalTreatment of patientsExpression of CD19Imatinib-resistant clonesMechanisms of progressionKinase inhibitor imatinibPresence of imatinibConcentrations of imatinib