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 regressionSuppressor of Cytokine Signaling (SOCS) Molecules Are Critical to Balance Oncogenic Signaling Strength in Ph+ ALL.
Chen Z, Geng H, Klemm L, Buchner M, Hemati K, Shojaee S, Alexander W, Carroll W, Willman C, Muschen M. Suppressor of Cytokine Signaling (SOCS) Molecules Are Critical to Balance Oncogenic Signaling Strength in Ph+ ALL. Blood 2012, 120: 2563. DOI: 10.1182/blood.v120.21.2563.2563.Peer-Reviewed Original ResearchBCR-ABL1Leukemia cellsTherapeutic targetSurvival rateP-STAT5Acute lymphoblastic leukemia cellsFree survival rateOverall survival rateHigh expression levelsG0/G1 cell cycle arrestRole of SOCS2Course of diseaseMRNA levelsAdditional therapeutic targetsNOD-SCID miceInducible deletionG1 cell cycle arrestLymphoblastic leukemia cellsExpression levelsCellular senescenceCOG trialsLeukemia regressionExpression of SOCS2Poor outcomeJAK/STAT pathway
2011
Targeting Inhibitory Phosphatases in Tyrosine Kinase-Driven Leukemias
Shojaee S, Buchner M, Geng H, Silvia B, Koeffler P, Muschen M. Targeting Inhibitory Phosphatases in Tyrosine Kinase-Driven Leukemias. Blood 2011, 118: 1382. DOI: 10.1182/blood.v118.21.1382.1382.Peer-Reviewed Original ResearchCell deathReactive oxygen speciesInducible deletionLeukemia cellsTyrosine kinase signalingActivation signalsSmall molecule inhibitionSubsequent cell deathMultiple new targetsLeukemia cell deathBCR-ABL1 oncogeneCytoplasmic tailKinase signalingTransplant recipient miceInduction of CreTyrosine kinase inhibitorsCellular senescenceMolecule inhibitionTyrosine kinasePTPN6Drastic upregulationINPP5DCurrent tyrosine kinase inhibitorsPTENDeletionDUSP6-Mediated Negative Feedback to Oncogenic Tyrosine Kinase Signaling Prevents Excessive Accumulation of ROS and Enables Leukemia Cell Survival
Shojaee S, Buchner M, Geng H, Melnick A, Gery S, Molkentin J, Koeffler P, Muschen M. DUSP6-Mediated Negative Feedback to Oncogenic Tyrosine Kinase Signaling Prevents Excessive Accumulation of ROS and Enables Leukemia Cell Survival. Blood 2011, 118: 1479. DOI: 10.1182/blood.v118.21.1479.1479.Peer-Reviewed Original ResearchCellular senescenceEffects of BCIProtein levelsCpG methylation analysisLeukemia cellsOncogene-induced senescenceGene expression changesLineage leukemiaCpG methylation levelsOncogenic tyrosine kinasesPharmacological inhibitionTyrosine kinase activityActivation of p53Small molecule inhibitorsBone marrow progenitor cellsGenetic experimentsDUSP6 functionLeukemia cell survivalTherapeutic targetB-cell lymphoma cell linesMarrow progenitor cellsNormal growth kineticsHigh ROS levelsKinase activityPromoter region
2010
The 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