2015
Targeting of Quiescent and Proliferating CML Stem Cells By DNA Repair Inhibitors
Sullivan K, Bolton-Gillespie E, Nieborowska-Skorska M, Cerny-Reiterer S, Valent P, Muschen M, Pomerantz R, Mazin A, Skorski T. Targeting of Quiescent and Proliferating CML Stem Cells By DNA Repair Inhibitors. Blood 2015, 126: 50. DOI: 10.1182/blood.v126.23.50.50.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia stem cellsTyrosine kinase inhibitorsChronic myeloid leukemiaCML cellsBCR-ABL1Myeloid leukemiaAnti-leukemia effectSimultaneous targetingCML leukemia stem cellsNew treatment modalitiesPARP1 inhibitorsCML stem cellsNormal counterpartsDouble knockout miceAdditional chromosomal aberrationsTKI-resistant BCRStem cellsBristol-Myers SquibbTKI therapyDisease relapseChronic phaseGood respondersCML patientsTreatment modalities
2010
Targeting Survivin In Recalcitrant Acute Lymphoblastic Leukemia
Park E, Jiang E, Hsieh Y, Klemm L, Duy C, Conway E, Pelus L, Crispino J, Loh M, Kang E, Koo H, Yang A, Heisterkamp N, Kahn M, Muschen M, Kim Y. Targeting Survivin In Recalcitrant Acute Lymphoblastic Leukemia. Blood 2010, 116: 3263. DOI: 10.1182/blood.v116.21.3263.3263.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaMedian survival timeLymphoblastic leukemiaLong-term side effectsNucleic acid antisense oligonucleotideRelapse of leukemiaSurvivin shRNASingle-agent treatmentNew treatment modalitiesNOD/SCIDEvaluation of survivinInhibition of survivinCFU assayBone marrow cellsGFP controlFunction studiesKnockout mouse modelOverexpression of survivinAmgen IncLNA treatmentLeukemia relapseKnockdown of survivinTreatment modalitiesCurrent treatmentMouse modelAdjuvant CD49d Blockade Eradicates Chemoresistant ALL
Hsieh Y, Park E, Jiang E, Dauber K, Chudziak D, Schaefer P, Klemm L, Scharman C, Kang E, Koo H, Loh M, Hofmann W, Heisterkamp N, Muschen M, Shimada H, Bonig H, Kim Y. Adjuvant CD49d Blockade Eradicates Chemoresistant ALL. Blood 2010, 116: 869. DOI: 10.1182/blood.v116.21.869.869.Peer-Reviewed Original ResearchAcute lymphocytic leukemiaNOD/SCID miceBone marrow cellsSCID miceSurvival timeB-lineage acute lymphocytic leukemiaCounter-receptor VCAM-1Drug resistanceNOD/SCID xenograft modelLong-term side effectsMarrow cellsChemotherapy-resistant leukemiaDose-limiting toxicityLeukemia cellsSaline-treated groupCell adhesion-mediated drug resistanceMedian survival timeImmunocompetent mouse modelRelapse of leukemiaSCID xenograft modelAcute lymphoblastic leukemiaMurine leukemiaProlonged survival timeNew treatment modalitiesAdhesion-mediated drug resistance
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
Preclinical Evaluation of Adjuvant Therapy with AMD3100 for Drug Resistant Philadelphia Chromosome Positive and Negative ALL
Jiang E, Yu M, Hsieh Y, DeLaTorre B, Kadavallore A, Scharman C, Park E, Yang A, Muschen M, Groffen J, Heisterkamp N, Kim Y. Preclinical Evaluation of Adjuvant Therapy with AMD3100 for Drug Resistant Philadelphia Chromosome Positive and Negative ALL. Blood 2008, 112: 2922. DOI: 10.1182/blood.v112.11.2922.2922.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaNOD/SCIDDrug-resistant leukemia cellsResistant leukemia cellsLeukemia cellsPreclinical evaluationPre-clinical xenograft modelNOD/SCID miceAcute lymphoblastic leukemia cellsCombination of AMD3100Different chemotherapeutic regimensNew treatment modalitiesLong-term survivalPrimary lymphoid organsLymphoblastic leukemia cellsTail vein injectionFurther preclinical evaluationCXCL12-CXCR4 interactionProgression of leukemiaB cell precursorsHigh death rateInteraction of CXCL12Clear beneficial effectPhiladelphia Chromosome PositiveBone marrow fibroblasts
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