2021
Beta-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
mTOR Kinase Inhibitors Enhance Efficacy of TKIs in Preclinical Models of Ph-like B-ALL
Gotesman M, Vo T, Mallya S, Zhang Q, Shi C, Müschen M, Weinstock D, Mullighan C, Tasian S, Konopleva M, Fruman D. mTOR Kinase Inhibitors Enhance Efficacy of TKIs in Preclinical Models of Ph-like B-ALL. Blood 2016, 128: 2763. DOI: 10.1182/blood.v128.22.2763.2763.Peer-Reviewed Original ResearchEvent-free survivalTOR-KIsPDX modelsBone marrowInhibitor monotherapyInhibitor therapyMurine bone marrowPatient-derived xenograft modelsTyrosine kinase inhibitor imatinibCompelling preclinical rationaleRearrangements of CRLF2Daily oral gavageEnd of treatmentKinase inhibitor therapyPrior preclinical studiesKinase inhibitor imatinibPI3K/mTORMouse bone marrow cellsBone marrow cellsNormal mouse bone marrow cellsReata PharmaceuticalsTKI dasatinibMost patientsLeukemia burdenPreclinical rationale