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 progenitorsIkaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621)
Schjerven H, Eggesbo L, Lindeman I, Muschen M. Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621). The Journal Of Immunology 2015, 194: 131.19-131.19. DOI: 10.4049/jimmunol.194.supp.131.19.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesSuppressor functionDNA-binding zinc fingersTumor suppressorGenome-wide expression analysisHuman preZinc finger transcription factorFinger transcription factorIndirect target genesDownstream target genesB cell developmentImportant tumor suppressorRole of IkarosProper hematopoiesisZinc fingerChIP-seqRNA-seqTranscription factorsPatient-derived preExpression analysisPotential roleIkarosGenesIkaros expression
2014
IFITM3 (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 phaseIL2RA (CD25) Recruits Inhibitory Phosphatases to the Cell Membrane and Mediates Negative Feedback Control of STAT5 Signaling in Acute Lymphoblastic Leukemia
Geng H, Lee J, Chen Z, Masouleh B, Hurtz C, Park E, Xiao G, Parekh S, Kornblau S, Melnick A, Paietta E, Muschen M. IL2RA (CD25) Recruits Inhibitory Phosphatases to the Cell Membrane and Mediates Negative Feedback Control of STAT5 Signaling in Acute Lymphoblastic Leukemia. Blood 2014, 124: 788. DOI: 10.1182/blood.v124.21.788.788.Peer-Reviewed Original ResearchCD25 expressionB cell developmentClinical outcomesPoor overall clinical outcomeHuman prePatient-derived preHigh-risk subsetNegative feedback controlTime of diagnosisOverall clinical outcomePoor clinical outcomeHigh-risk subtypesLeukemia initiationAcute lymphoblastic leukemiaCell developmentPhosphorylation levelsImmune precipitationColony formation capacityTransplant recipientsTyrosine kinaseTransplant settingLymphoblastic leukemiaIL-2Cell surface expressionNormal B cell developmentPTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells
Shojaee S, Cazzaniga V, Schjerven H, Buchner M, Hurtz C, Geng H, Hochhaus A, Cazzaniga G, Melnick A, Kornblau S, Graeber T, Muschen M. PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells. Blood 2014, 124: 262. DOI: 10.1182/blood.v124.21.262.262.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAlleles of PTENDeletion of PTENPI3K-Akt pathwayPI3K-Akt signalingGlucocorticoid resistanceHuman preSmall molecule inhibitorsBCR-ABL1Expression levelsMyeloid lineage leukemiasPatient-derived prePTEN deletionT-cell acute lymphoblastic leukemiaCell acute lymphoblastic leukemiaHigh expression levelsLeukemia cellsTime of diagnosisPoor clinical outcomeCell deathMature B-cell lymphomasPTEN inhibitionHuman cancersLeukemia/lymphomaB-cell lymphoma
2007
Preclinical Evaluation of CBP/β-catenin Inhibition as a New Strategy for Drug Resistant Acute Lymphoblastic Leukemia.
Kim Y, Park E, Lorentzen C, De La Torre B, Hsieh Y, Whang H, Klemm L, Nguyen C, McMillan M, Teo J, Muschen M, Kahn M. Preclinical Evaluation of CBP/β-catenin Inhibition as a New Strategy for Drug Resistant Acute Lymphoblastic Leukemia. Blood 2007, 110: 1596. DOI: 10.1182/blood.v110.11.1596.1596.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaMedian survival timeStandard chemotherapyICG-001Expression of survivinLymphoblastic leukemiaLeukemia cellsXenograft modelDrug-resistant acute lymphoblastic leukemiaSmall molecule inhibitor ICG-001NOD/SCID xenograft modelHuman preCBP/β-cateninPromising therapeutic principleBlood count analysisSCID xenograft modelSurvival of miceNovel therapeutic optionsNew treatment modalitiesΒ-cateninDrug-resistant leukemia cellsΒ-catenin inhibitionHigh death rateResistant leukemia cellsSurvivin mRNA expression