2019
Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation
Cosgun K, Deb G, Yang X, Xiao G, Sadras T, Lee J, Chan L, Kume K, Yang L, Geng H, Chan J, Song J, Jumaa H, Polson A, Clevers H, Müschen M. Lgr5 Functions As a Critical Negative Regulator of Wnt/β-Catenin Signaling and Is Essential for B-Lymphopoiesis and Malignant B-Cell Transformation. Blood 2019, 134: 748. DOI: 10.1182/blood-2019-127263.Peer-Reviewed Original ResearchB-cell lineage acute lymphoblastic leukemiaWnt/β-catenin signalingΒ-catenin signalingNuclear β-cateninAntibody-drug conjugatesB cell developmentB cell survivalΒ-cateninB lymphopoiesisFunction of LGR5Median mRNA levelsTime of diagnosisPoor clinical outcomeRole of LGR5Acute lymphoblastic leukemiaB-cell lymphomaLeukemia initiating cellsWnt/β-cateninHigh surface expressionMalignant B-cell transformationCell linesB cell precursorsTypes of cancerHuman colon cancer cell linesB-cell lineage
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
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