2022
SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies
Leveille E, Chan LN, Mirza AS, Kume K, Müschen M. SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies. Cellular Signalling 2022, 94: 110331. PMID: 35398488, DOI: 10.1016/j.cellsig.2022.110331.Peer-Reviewed Original ResearchConceptsChronic lymphocytic leukemiaB-cell malignanciesT cell receptorB cell receptorB-cell chronic lymphocytic leukemiaPathological B-cellsPoor clinical outcomeAcute lymphoblastic leukemiaExpression of SykT lymphocyte developmentClinical outcomesAggressive diseaseActivation of NFATAutoimmune diseasesLymphoblastic leukemiaT lymphocytesLymphocytic leukemiaCell lymphomaLymphoid malignanciesB cellsPI3K-pathwayOncogenic driversMalignancyNegative selectionPremalignant cells
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 leukemia
2020
Signalling input from divergent pathways subverts B cell transformation
Chan LN, Murakami MA, Robinson ME, Caeser R, Sadras T, Lee J, Cosgun KN, Kume K, Khairnar V, Xiao G, Ahmed MA, Aghania E, Deb G, Hurtz C, Shojaee S, Hong C, Pölönen P, Nix MA, Chen Z, Chen CW, Chen J, Vogt A, Heinäniemi M, Lohi O, Wiita AP, Izraeli S, Geng H, Weinstock DM, Müschen M. Signalling input from divergent pathways subverts B cell transformation. Nature 2020, 583: 845-851. PMID: 32699415, PMCID: PMC7394729, DOI: 10.1038/s41586-020-2513-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell Line, TumorCell Transformation, NeoplasticEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansLeukemia, B-CellMiceProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycSignal TransductionSTAT5 Transcription FactorConceptsPre-B cell receptorPrincipal oncogenic driverDivergent pathwaysSignal transduction proteinsPro-B cell stageSingle-cell mutationTranscription factor MYCOncogenic driversDivergent signaling pathwaysSingle oncogenic pathwayCentral oncogenic driverMore mature cellsGenetic reactivationTranscriptional programsB-cell transformationProtein kinasePathway componentsERK activationIndividual mutationsOncogenic STAT5Signaling pathwaysCell transformationCytokine receptorsGenetic lesionsDivergent circuits
2019
Signaling Input from Divergent Pathways Subverts Malignant B-Cell Transformation
Chan L, Murakami M, Caesar R, Hurtz C, Kume K, Sadras T, Shojaee S, Pölönen P, Ugale A, Lee J, Cosgun K, Geng H, Heinäniemi M, Lohi O, Wiita A, Izraeli S, Weinstock D, Müschen M. Signaling Input from Divergent Pathways Subverts Malignant B-Cell Transformation. Blood 2019, 134: 3944. DOI: 10.1182/blood-2019-130774.Peer-Reviewed Original ResearchB-cell transformationPrincipal oncogenic driverMalignant B-cell transformationOncogenic driversMalignant transformationNormal B cellsDrug-resistant cancersCentral oncogenic driverCurrent treatmentB cellsPharmacological reactivationSingle oncogenic pathwaySmall molecule agonistsSurface receptorsAdvisory CommitteeB cell receptorERK signal pathwayNormal B cell developmentTreatment responseRare caseDivergent signaling pathwaysSolid tumorsB cell developmentFatal diseaseMolecule agonists