2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3
2019
Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies
Sadras T, Martin M, Kim-Sing L, Cutler J, Lenz G, Knapp A, Ghergus D, Delmotte F, Schleiss C, Korganow A, Soulas-Sprauel P, Chen Z, Pandey A, Weinstock D, Jumaa H, Meffre E, Martin T, Müschen M. Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies. Blood 2019, 134: 295. DOI: 10.1182/blood-2019-128999.Peer-Reviewed Original ResearchB-cell chronic lymphocytic leukemiaNegative B cell selectionB cellsB-cell malignanciesB cell selectionCo-expressing cellsT cellsBCR-stimulated B cellsZAP70 expressionMultiple B-cell malignanciesLymphoma cellsAutoreactive BCRsCentral tolerance checkpointsCell deathT cell populationsB cell compartmentChronic lymphocytic leukemiaProximity ligation assayB-cell lymphoma cellsMantle cell lymphomaTumor B cellsExpression of ZAP70Human B-cell lymphoma cellsImmature B cellsDevelopment of leukemia