2016
Identification of the Energy Stress Sensor AMPK As Therapeutic Target in Acute Lymphoblastic Leukemia
Chan L, Lee J, Cosgun K, Geng H, Xiao G, Chen Z, Ernst T, Hochhaus A, Müschen M. Identification of the Energy Stress Sensor AMPK As Therapeutic Target in Acute Lymphoblastic Leukemia. Blood 2016, 128: 2771. DOI: 10.1182/blood.v128.22.2771.2771.Peer-Reviewed Original ResearchChronic myeloid leukemiaAcute lymphoblastic leukemiaMyeloid leukemiaTransplant recipient miceB-cell lineageLKB1/AMPKLymphoblastic leukemiaRecipient miceCML cellsTherapeutic targetLong-term disease-free survivalPhiladelphia chromosome-positive acute lymphoblastic leukemiaB-cell lineage leukemiaPatient-derived preDisease-free survivalInducible deletionNovel therapeutic targetGlycolytic activityBCR-ABL1 tyrosine kinaseNovel therapeutic avenuesATP levelsMitochondrial functionCell deathInitial remissionClinical characteristics
2014
BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia
Hurtz C, Geng H, Xiao G, Loh M, Ye B, Melnick A, Muschen M. BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia. Blood 2014, 124: 3570. DOI: 10.1182/blood.v124.21.3570.3570.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaAcute lymphoblastic leukemiaLymphoblastic leukemiaMouse modelRas-ERK pathwayB-cell lineage leukemiaChildhood acute lymphoblastic leukemiaExpression levelsLarge B-cell lymphomaInhibition of BCL6Patient-derived preB cell lineage cellsBCL6 expressionConventional cytotoxic therapyNovel mouse modelBCL6 functionB-cell lymphomaGenetic mouse modelsMRNA expression levelsMEK inhibitor PD325901Lineage-specific deletionPre-B-cell transformationCell transformationInitial remissionQuantitative RT-PCRBACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia
Park E, Swaminathan S, Sadiyah M, Igarashi K, Melnick A, Muschen M. BACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia. Blood 2014, 124: 513. DOI: 10.1182/blood.v124.21.513.513.Peer-Reviewed Original ResearchLymphoid blast crisisFate decisionsB-cell lineageCML-like diseaseCell lineagesTumor suppressorCML cellsBCR-ABL1Transcription factorsTransplant recipientsLineage-specific transcription factorsChronic phaseB-cell-specific transcription factorCell-specific transcription factorsBlast crisisPre-B cell receptor checkpointB-cell lineage leukemiaPrimary human CML cellsRole of Bach2Multi-lineage progenitor cellsEmpty vector controlGene expression analysisSelective proliferative advantagePotent tumor suppressorCML chronic phaseThe Linker Protein GAS7 Negatively Regulates Pre-B Cell Differentiation and Amplifies Proliferation and Survival Signals in Acute Lymphoblastic Leukemia
Lee J, Buchner M, Geng H, Swaminathan S, Park E, Park A, Lin-Chao S, So C, Muschen M. The Linker Protein GAS7 Negatively Regulates Pre-B Cell Differentiation and Amplifies Proliferation and Survival Signals in Acute Lymphoblastic Leukemia. Blood 2014, 124: 3777. DOI: 10.1182/blood.v124.21.3777.3777.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaTyrosine kinase inhibitorsLymphoblastic leukemiaBCR-ABL1B-cell lineage leukemiaPre-B cell differentiationTyrosine kinase inhibitor treatmentPediatric acute lymphoblastic leukemiaTreatment-related acute myeloid leukemiaAcute myeloid leukemiaPre-B cell receptor checkpointKinase inhibitor treatmentEffects of Stat5Spontaneous IgNormal B cell developmentMyeloid leukemiaB cell progenitorsBone marrowCell differentiationInhibitor treatmentB cell developmentLeukemiaSelf-renewal capacityConditional deletionKinase inhibitors
2013
Gas7 Induces The Proliferation Of Ph+ ALL Cells and Prevents The Differentiation Of Early B Cell Progenitors Into CD25high Small Pre-B Cells
Lee J, Buchner M, Geng H, Swaminathan S, Park E, Klemm L, Lin-Chao S, So C, Muschen M. Gas7 Induces The Proliferation Of Ph+ ALL Cells and Prevents The Differentiation Of Early B Cell Progenitors Into CD25high Small Pre-B Cells. Blood 2013, 122: 2506. DOI: 10.1182/blood.v122.21.2506.2506.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAcute myeloid leukemiaTyrosine kinase inhibitorsB cell progenitorsBCR-ABL1B cell developmentEarly B cell developmentCell progenitorsB-cell lineage leukemiaPediatric acute lymphoblastic leukemiaMotor neuron numberBone marrow B-cell progenitorsEffects of Stat5Growth arrest-specific gene 7Levels of p21Leukemia cell survivalExpression of intracellularLymphoblastic leukemiaIL7R expressionMyeloid leukemiaBone marrowB cellsInterleukin-7Pre B cellsSelf-renewal capacityInhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia
Chen Z, Shojaee S, Geng H, Lee J, Buchner M, Klemm L, Lowell C, Paietta E, Willman C, Carroll W, Melnick A, Jung J, Jumaa H, Coligan J, Bolland S, Mak T, Muschen M. Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia. Blood 2013, 122: 229. DOI: 10.1182/blood.v122.21.229.229.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaB cell receptorTyrosine kinase inhibitorsInhibitory receptorsTherapeutic targetB cellsBCR-ABL1Survival rateB-cell lineage leukemiaCell deathAuto-reactive clonesFree survival rateLeukemia cellsOverall survival rateWorse clinical outcomesG0/G1 cell cycle arrestAdditional therapeutic targetsCycle arrestAvailable therapeutic interventionsG1cell cycle arrestPotential therapeutic targetG1 cell cycle arrestOncogenic tyrosine kinasesNovel small molecule inhibitorCellular senescence
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 precursorsSOX4 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 DNA
2010
The Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia
Shojaee S, Garcia C, Wu H, Muschen M. The Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia. Blood 2010, 116: 513. DOI: 10.1182/blood.v116.21.513.513.Peer-Reviewed Original ResearchB-cell lineage leukemiaCML-like leukemiaChronic myeloid leukemiaB-cell lineageAcute lymphoblastic leukemiaDeletion of PTENLeukemia stem cellsCell cycle arrestT-cell lineageBCR-ABL1Myeloid leukemiaB cell precursorsCellular senescencePI3K/AktCell lineagesLeukemia cell growthEmpty vector controlLeukemia cellsTumor suppressorCML cellsSolid tumorsCycle arrestWestern blotCell precursorsStem cells
2006
SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells
Sprangers M, Feldhahn N, Liedtke S, Jumaa H, Siebert R, Müschen M. SLP65 deficiency results in perpetual V(D)J recombinase activity in pre-B-lymphoblastic leukemia and B-cell lymphoma cells. Oncogene 2006, 25: 5180-5186. PMID: 16636677, DOI: 10.1038/sj.onc.1209520.Peer-Reviewed Original ResearchConceptsLymphoblastic leukemiaRecombinase activityRAG1/2 expressionB-cell lineage leukemiaDouble-strand break eventsLymphoma cellsSecondary genetic aberrationsB-cell lymphomaB-cell lymphoma cellsB-lymphoid malignanciesB-cell malignanciesB cell receptorVH gene rearrangementsMalignant progressionLeukemiaFrequent featureGenetic aberrationsGene rearrangementsCells resultsRearrangement activityLineage leukemiaMalignancyVH replacementDeficiencyExpression