2016
PP2A Balances Glucose Metabolism and Foxo Activation to Maintain Cellular Redox Homeostasis in Acute Lymphoblastic Leukemia
Xiao G, Chen Z, Daniel B, Chan L, Geng H, Jiang X, Müschen M. PP2A Balances Glucose Metabolism and Foxo Activation to Maintain Cellular Redox Homeostasis in Acute Lymphoblastic Leukemia. Blood 2016, 128: 1056. DOI: 10.1182/blood.v128.22.1056.1056.Peer-Reviewed Original ResearchLineage-specific rolesPro-survival roleLB-100PP2A subunitsRedox homeostasisH2AX phosphorylationUnexpected rolePI3K-AktFunction of PP2AProtein phosphatase 2ACellular redox homeostasisSer/ThrCatalytic subunit CAnti-oxidant gene expressionS6 ribosomal proteinHigh glycolytic fluxRescue effectGrowth competition assaysLeukemia cellsPentose phosphate pathway fluxHigher reactive oxygen species (ROS) levelsReduced cell growthPP2A functionSmall molecule inhibitorsFOXO factors
2015
IFITM3 (CD225) Links the B Cell Antigen CD19 to PI3K-AKT Signaling in Human ALL Cells
Lee J, Geng H, Chen Z, Eugene P, Klemm L, Bailey C, Muschen M. IFITM3 (CD225) Links the B Cell Antigen CD19 to PI3K-AKT Signaling in Human ALL Cells. Blood 2015, 126: 1325. DOI: 10.1182/blood.v126.23.1325.1325.Peer-Reviewed Original ResearchTime of diagnosisPI3K-Akt signalingPI3K-AktHuman preSurface expressionAgonistic antibodiesB-cell antigen CD19Patient-derived preRelapse-free survivalMRNA levelsChimeric antigen receptorMedian expression levelPI3K p110δSurface receptorsColony formation capacityMRD statusInduction chemotherapyImmunotherapy approachesAntigen CD19Cell cycle arrestCell receptor complexClinical trialsCD19 expressionHigh riskB cell progenitors
2014
Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis
Xiao G, Geng H, Chan L, Chen Z, Muschen M. Divergent Lineage-Specific Functions of PP2A in Chronic Phase CML and Lymphoid Blast Crisis. Blood 2014, 124: 3128. DOI: 10.1182/blood.v124.21.3128.3128.Peer-Reviewed Original ResearchFunction of PP2ACell lineagesB cell developmentB-cell lineageSer/Thr phosphataseCell developmentPI3K-AktEarly B cell developmentProtein phosphatase 2ALineage-specific functionsNormal B cell developmentChronic phase chronic myeloid leukemiaLineage-specific requirementGlycolytic fluxPre-B cell receptor checkpointMyeloid lineagePhase chronic myeloid leukemiaChronic myeloid leukemiaRegulation of AktS6 ribosomal proteinHigh glycolytic fluxRapid cell deathLymphoid blast crisisImportant tumor suppressorColony formation capabilityIFITM3 (CD225) Regulates CD19 Surface Expression and CD19-Mediated Activation of PI3K Signaling in Pre-B Acute Lymphoblastic Leukemia Cells
Lee J, Geng H, Chen Z, Park E, Park A, Klemm L, Bailey C, Muschen M. IFITM3 (CD225) Regulates CD19 Surface Expression and CD19-Mediated Activation of PI3K Signaling in Pre-B Acute Lymphoblastic Leukemia Cells. Blood 2014, 124: 1070. DOI: 10.1182/blood.v124.21.1070.1070.Peer-Reviewed Original ResearchCD19-specific chimeric antigen receptorTime of diagnosisB cell progenitorsPI3K-AktSurface expressionCell cycle arrestC-myc expressionCD19 expressionCell progenitorsB cellsHuman preAcute lymphoblastic leukemia cellsLow-dose AdriamycinPatient-derived preSignificant inhibitionRelapse-free survivalG0/G1 cell cycle arrestMRNA levelsChimeric antigen receptorExpression of CD19Cycle arrestBCR-ABL1 activityG1 cell cycle arrestLymphoblastic leukemia cellsG0/G1 phase