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 phase
2013
Ifitm3 (CD225) Mediates CD19-Dependent Survival and Proliferation During Normal B Cell Development and In Ph+ ALL
Lee J, Geng H, Chen Z, Park E, Klemm L, Bailey C, Muschen M. Ifitm3 (CD225) Mediates CD19-Dependent Survival and Proliferation During Normal B Cell Development and In Ph+ ALL. Blood 2013, 122: 2505. DOI: 10.1182/blood.v122.21.2505.2505.Peer-Reviewed Original ResearchB cell progenitorsC-myc expressionOverall survivalCell cycle arrestCell progenitorsB cellsBCR-ABL1Minimal residual disease statusResidual disease statusSignificant inhibitionTime of diagnosisG0/G1 cell cycle arrestHigh expression levelsPoor overall survivalExpression of CD19Treatment of adriamycinSurface expressionCycle arrestBCR-ABL1 activityG1 cell cycle arrestExpression levelsG0/G1 phaseCellular senescenceLow surface expressionLevels of p53Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia
Chen Z, Shojaee S, Geng H, Lee J, Buchner M, Klemm L, Lowell C, Paietta E, Willman C, Carroll W, Melnick A, Jung J, Jumaa H, Coligan J, Bolland S, Mak T, Muschen M. Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia. Blood 2013, 122: 229. DOI: 10.1182/blood.v122.21.229.229.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaB cell receptorTyrosine kinase inhibitorsInhibitory receptorsTherapeutic targetB cellsBCR-ABL1Survival rateB-cell lineage leukemiaCell deathAuto-reactive clonesFree survival rateLeukemia cellsOverall survival rateWorse clinical outcomesG0/G1 cell cycle arrestAdditional therapeutic targetsCycle arrestAvailable therapeutic interventionsG1cell cycle arrestPotential therapeutic targetG1 cell cycle arrestOncogenic tyrosine kinasesNovel small molecule inhibitorCellular senescence
2012
ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL
Chen Z, Geng H, Buchner M, Klemm L, Hemati K, Shojaee S, Tak M, Coligan J, Carroll W, Willman C, Muschen M. ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL. Blood 2012, 120: 291. DOI: 10.1182/blood.v120.21.291.291.Peer-Reviewed Original ResearchBCR-ABL1Leukemia cellsInhibitory receptorsLeukemia cell deathTherapeutic targetSurvival rateCellular senescenceAcute lymphoblastic leukemia cellsFree survival rateOverall survival rateG0/G1 cell cycle arrestMRNA levelsAdditional therapeutic targetsNOD-SCID miceNormal bone marrow samplesBone marrow samplesCycle arrestHalf of casesG1cell cycle arrestLymphoblastic leukemia cellsG1 cell cycle arrestCell deathColony forming assaysCOG trialsLeukemia regression
2010
IKAROS and BCL6 Limit Pre-B Cell Expansion and Prevent Leukemogenesis Downstream of the Pre-B Cell Receptor
Nahar R, Ramezani-Rad P, Duy C, Dovat S, Ye B, Melnick A, Muschen M. IKAROS and BCL6 Limit Pre-B Cell Expansion and Prevent Leukemogenesis Downstream of the Pre-B Cell Receptor. Blood 2010, 116: 146. DOI: 10.1182/blood.v116.21.146.146.Peer-Reviewed Original ResearchPre-B cell receptorCell cycle arrestCell cycle progressionTumor suppressorCycle arrestTumor suppressionIkaros functionCycle progressionNegative cell cycle regulationSignaling leadsDephosphorylation of STAT5Cell receptorIkaros expressionBCL6 transcriptional repressorGenome-wide ChIPPre-B cell expansionCell cycle regulationSubsequent cell cycle arrestCentral mediatorOverexpression of MYCProliferation downstreamTranscriptional repressionGenetic experimentsTranscriptional repressorTranscriptional activationSYK Is a Tumor Suppressor In Pre-B Cell Acute Lymphoblastic Leukemia and Not a Therapeutic Target
Ng C, Nahar R, Elliott E, Lowell C, Muschen M. SYK Is a Tumor Suppressor In Pre-B Cell Acute Lymphoblastic Leukemia and Not a Therapeutic Target. Blood 2010, 116: 4199. DOI: 10.1182/blood.v116.21.4199.4199.Peer-Reviewed Original ResearchDeletion of SykPre-B leukemia cellsAcute lymphoblastic leukemiaPre-B cell receptor functionB-cell lymphomaImatinib treatmentTumor-suppressive effectsRole of SykPre-B cell receptorCell cycle arrestBCR-ABL1Cell receptorCritical survival signalsLeukemia cellsCell receptor signalingLymphoblastic leukemiaCell lymphomaSuppressive effectCycle arrestSyk tyrosine kinaseReceptor functionPre-B-cell acute lymphoblastic leukemiaWestern blotReceptor signalingPre-B cell receptor expressionThe Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia
Shojaee S, Garcia C, Wu H, Muschen M. The Tumor Suppressor PTEN Is Required to Prevent Cellular Senescence and Cell Cycle Arrest In B Cell Lineage and Chronic Myeloid Leukemia. Blood 2010, 116: 513. DOI: 10.1182/blood.v116.21.513.513.Peer-Reviewed Original ResearchB-cell lineage leukemiaCML-like leukemiaChronic myeloid leukemiaB-cell lineageAcute lymphoblastic leukemiaDeletion of PTENLeukemia stem cellsCell cycle arrestT-cell lineageBCR-ABL1Myeloid leukemiaB cell precursorsCellular senescencePI3K/AktCell lineagesLeukemia cell growthEmpty vector controlLeukemia cellsTumor suppressorCML cellsSolid tumorsCycle arrestWestern blotCell precursorsStem cells