2018
SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia
Ecker V, Braun M, Neumayer T, Muschen M, Ruland J, Buchner M. SHIP1 Inhibition As Novel Therapeutic Approach in Chronic Lymphocytic Leukemia. Blood 2018, 132: 894. DOI: 10.1182/blood-2018-99-117053.Peer-Reviewed Original ResearchChronic lymphocytic leukemiaMyeloid-derived suppressor cellsSecondary lymphoid organsImmune cell functionPeripheral bloodCLL cellsLymph nodesMalignant CLL cellsB cellsT cellsImmune responseLymphoid organsLymphocytic leukemiaSmall molecule inhibitorsSHIP1 inhibitionAge-matched healthy donorsAnti-tumor immune responsePharmacological inhibitionCell deathCLL peripheral bloodTreatment-related toxicityImmunoglobulin-producing plasma cellsRegulatory T cellsCell functionCLL cell death
2015
Overcoming Drug Resistance of Pre-B ALL Cells By Targeting Integrin alpha6 Associated Cell-Adhesion Mediated Drug Resistance Using a Novel Antibody, P5G10
Gang E, Hsieh Y, Kim H, Duchartre Y, Stephanie S, Muschen M, Wayner E, Heisterkamp N, Bonig H, Kim Y. Overcoming Drug Resistance of Pre-B ALL Cells By Targeting Integrin alpha6 Associated Cell-Adhesion Mediated Drug Resistance Using a Novel Antibody, P5G10. Blood 2015, 126: 2525. DOI: 10.1182/blood.v126.23.2525.2525.Peer-Reviewed Original ResearchMinimal residual diseaseTyrosine kinase inhibitorsPeripheral bloodDrug resistanceFlow cytometryLeukemia cellsRecipient miceHuman CD45Bone marrowBCR-ABL1NOD/SCID miceControl recipient miceCell adhesion-mediated drug resistanceAdhesion-mediated drug resistanceNovel therapeutic targetControl-treated cellsCell-bearing miceChemotherapy-resistant cellsPercentage of adherenceLaminin-1Integrin alpha 6Mesenchymal stromal cellsNormal hematopoietic cellsOvercoming Drug ResistanceUntreated mice
2013
Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells
Nieborowska-Skorska M, Slupianek A, Hoser G, Bolton-Gillespie E, Tulin A, Cerny-Reiterer S, Valent P, Muschen M, Sykes S, Skorski T. Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells. Blood 2013, 122: 810. DOI: 10.1182/blood.v122.21.810.810.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia progenitor cellsLeukemia stem cellsImatinib-naïveLeukemia cellsAML1-ETOBCR-ABL1PARP1 inhibitorsProgenitor cellsNormal cellsAnti-leukemia effectPositive AML cellsBCR-ABL1 T315I mutationInhibited colony formationAnti-proliferative effectsPARP inhibitor olaparibStem cellsModest inhibitory effectInhibition of PARPPeripheral bloodDisease burdenBone marrow nicheClinical trialsAML cellsT315I mutation
2009
Targeting Survivin Using ICG-001 May Overcome Drug Resistance in Primary B-Cell Acute Lymphoblastic Leukemia.
Jiang E, Park E, Scharman C, Hsieh Y, Kadavallore A, Nguyen C, Zhao Y, McMillan M, Groffen J, Heisterkamp N, Muschen M, Kahn M, Kim Y. Targeting Survivin Using ICG-001 May Overcome Drug Resistance in Primary B-Cell Acute Lymphoblastic Leukemia. Blood 2009, 114: 3072. DOI: 10.1182/blood.v114.22.3072.3072.Peer-Reviewed Original ResearchMedian survival timeAcute lymphoblastic leukemiaWhite blood cellsICG-001Control groupBlood cellsStandard chemotherapyRed blood cellsPeripheral bloodLymphoblastic leukemiaSmall molecule inhibitor ICG-001B-cell acute lymphoblastic leukemiaDrug resistanceCBP/β-cateninNormal hematopoiesisPromising therapeutic principleNormal white blood cellsConventional drug treatmentLeukemia cellsPrior intravenous injectionEnd of treatmentNovel therapeutic optionsNormal weight gainNew treatment modalitiesSubcutaneous osmotic pumps
2008
Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1
Trageser D, Duy C, Klemm L, Gruber T, Nahar R, Park E, Kim Y, Groffen J, Heisterkamp N, Hofmann W, Martinelli G, Williams R, Jumaa H, Muschen M. Pre-B Cell Receptor Signaling Prevents Leukemic Transformation by BCR-ABL1. Blood 2008, 112: 15. DOI: 10.1182/blood.v112.11.15.15.Peer-Reviewed Original ResearchFunctional pre-B cell receptorAcute lymphoblastic leukemiaBCR-ABL1Pre-B cell receptorCell receptorBone marrowPre-B cell receptor functionTransgenic miceLeukemic transformationLeukemic growthNOD/SCID miceWeight lossLeukemia cellsReceptor selectionTransgenic mouse modelSignificant weight lossPre-B cell receptor signalingBCR-ABL1 expressionSigns of diseaseSurvival signalsEarly B cell developmentLeukemic infiltrationSplenic enlargementCell receptor signalingPeripheral blood