2015
Identification of BCL6 As a Therapeutic Target in RAS-Driven Acute Lymphoblastic Leukemia
Li Q, Hurtz C, Shojaee S, Chen Z, Geng H, Xiao G, Loh M, Ye B, Melnick A, Muschen M. Identification of BCL6 As a Therapeutic Target in RAS-Driven Acute Lymphoblastic Leukemia. Blood 2015, 126: 556. DOI: 10.1182/blood.v126.23.556.556.Peer-Reviewed Original ResearchTime of relapseAcute lymphoblastic leukemiaLymphoblastic leukemiaTherapeutic targetNOD/SCID miceInhibition of BCL6Conventional cytotoxic therapyBCL6 functionComplementary mouse modelsTransplant recipient miceTranscriptional repressor BCL6P53-dependent senescenceMEK inhibitor PD325901Patient-derived cellsInitial remissionTransplant recipientsLeukemia relapseInitial diagnosisPathway lesionsCytotoxic therapyRecipient miceSCID miceSame patientFatal leukemiaMouse model
2013
Normal ABL1 Is a Tumor Suppressor and Therapeutic Target In BCR-ABL1–positive Leukemias
Dasgupta Y, Koptyra M, Nieborowska-Skorska M, Gillespie E, Stoklosa T, Hoser G, Wasik M, Muschen M, Richardson C, Skorski T. Normal ABL1 Is a Tumor Suppressor and Therapeutic Target In BCR-ABL1–positive Leukemias. Blood 2013, 122: 1466. DOI: 10.1182/blood.v122.21.1466.1466.Peer-Reviewed Original ResearchLeukemia stem cellsCML-CPBCR-ABL1Myeloid differentiationCML blast phaseTumor suppressorEffect of imatinibChronic myeloid leukemiaNovel therapeutic strategiesABL1 kinaseHigher clonogenic activityPositive CML cellsStem cellsBCR-ABL1 kinaseImatinib-treated cellsPotential tumor suppressorChronic phaseCML treatmentLSC compartmentMyeloid leukemiaSCID miceCML CD34Blastic transformationOxidative DNA damageT315I mutation
2010
BCL6 Is Required for the Maintenance of Leukemia-Initiating Cells In Chronic Myeloid Leukemia
Hurtz C, Duy C, Cerchietti L, Chatzi K, Park E, Klemm L, Kim Y, Kahn M, Braig M, Muller M, Hochhaus A, Ye B, Melnick A, Muschen M. BCL6 Is Required for the Maintenance of Leukemia-Initiating Cells In Chronic Myeloid Leukemia. Blood 2010, 116: 202. DOI: 10.1182/blood.v116.21.202.202.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaNOD/SCID miceChronic myeloid leukemiaHuman CML cellsLeukemia stem cellsTyrosine kinase inhibitorsCML cellsLeukemia-initiating cellsSCID miceMyeloid leukemiaCML patientsBCL6 expressionLeukemia stem cell maintenanceLSK cellsLarge B-cell lymphomaAbsence of Bcl6CML-initiating cellsCML-like leukemiaDistinct side populationStem cellsProtein levelsColony formationGene expression changesB-cell lymphomaLeukemia initiating cellsAdjuvant 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
2008
Aberrant Splicing of the SLP65 SH2 Domain Enables Pre-B Cell Transformation and Compromises the Leukemia-Suppressive Function of the Pre-B Cell Receptor
Duy C, Klemm L, Nahar R, van Essen P, Sprangers M, Kim Y, Park E, Martinelli G, Heisterkamp N, Hofmann W, Jumaa H, Muschen M. Aberrant Splicing of the SLP65 SH2 Domain Enables Pre-B Cell Transformation and Compromises the Leukemia-Suppressive Function of the Pre-B Cell Receptor. Blood 2008, 112: 294. DOI: 10.1182/blood.v112.11.294.294.Peer-Reviewed Original ResearchBCR-ABL1Pre-B cell receptorEarly pre-B cell stageCell receptorPre-B cell stageNOD/SCID miceLeukemia cellsPre-B cell receptor signalingSigns of diseaseSplice variantsEarly B cell developmentLeukemic infiltrationQuantitative RT-PCRCell receptor signalingCell receptor engagementSCID miceBone marrowB cell developmentMalignant transformationPre-B-cell transformationLeukemic growthCell transformationInduction of differentiationGermline mutationsMiceBCL6-Mediated Survival Signaling Promotes Drug-Resistance in BCRABL1- Driven Acute Lymphoblastic Leukemia
Duy C, Yu J, Cerchietti L, Klemm L, Nahar R, Kim Y, Heisterkamp N, Martinelli G, Hofmann W, Jumaa H, Melnick A, Ye B, Muschen M. BCL6-Mediated Survival Signaling Promotes Drug-Resistance in BCRABL1- Driven Acute Lymphoblastic Leukemia. Blood 2008, 112: 295. DOI: 10.1182/blood.v112.11.295.295.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaGerminal center B cellsImatinib treatmentBCR-ABL1Bone marrowB cellsLymphoblastic leukemiaHuman BCR-ABL1NOD/SCID miceFunction of Bcl6Inhibition of BCL6Low-dose imatinibBCL6 expressionLeukemia cellsP53 signalingProtein levelsCombination of imatinibGerminal center B cell survivalTail vein injectionNovel treatment conceptsTranscriptional repressor BCL6B cell survivalLow proliferation rateRecipient miceSCID mice