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
2014
BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia
Hurtz C, Geng H, Xiao G, Loh M, Ye B, Melnick A, Muschen M. BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia. Blood 2014, 124: 3570. DOI: 10.1182/blood.v124.21.3570.3570.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaAcute lymphoblastic leukemiaLymphoblastic leukemiaMouse modelRas-ERK pathwayB-cell lineage leukemiaChildhood acute lymphoblastic leukemiaExpression levelsLarge B-cell lymphomaInhibition of BCL6Patient-derived preB cell lineage cellsBCL6 expressionConventional cytotoxic therapyNovel mouse modelBCL6 functionB-cell lymphomaGenetic mouse modelsMRNA expression levelsMEK inhibitor PD325901Lineage-specific deletionPre-B-cell transformationCell transformationInitial remissionQuantitative RT-PCRSelf-Enforcing Feedback Activation Between BCL6 and Tonic Pre-B Cell Receptor Signaling in Acute Lymphoblastic Leukemia
Geng H, Hurtz C, Baumjohann D, Chen Z, Chen W, Ballabio E, Xiao G, Lee J, Deucher A, Qi Z, Huang C, Nahar R, Kweon S, Shojaee S, Chan L, Yu J, Tyner J, Chang B, Kornblau S, Bijl J, Ye B, Paietta E, Melnick A, Roeder R, Hunger S, Loh M, Milne T, Muschen M. Self-Enforcing Feedback Activation Between BCL6 and Tonic Pre-B Cell Receptor Signaling in Acute Lymphoblastic Leukemia. Blood 2014, 124: 284. DOI: 10.1182/blood.v124.21.284.284.Peer-Reviewed Original ResearchPre-BCR expressionB cell receptorInhibition of BCL6Patient-derived preTreatment of patientsMature B-cell lymphomasB-cell lymphomaPre-BCR signalingTCF3-PBX1Cell lymphomaMouse modelCell receptorDeletion of Bcl6Time of diagnosisBCL6 expressionPoor clinical outcomeAcute lymphoblastic leukemiaNovel mouse modelFeedback activationTranscription factor Bcl6Genetic mouse modelsB cell precursorsInhibition of SykHeavy chain expressionLineage-specific deletion
2011
BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia
Hurtz C, Hatzi K, Cerchietti L, Braig M, Park E, Kim YM, Herzog S, Ramezani-Rad P, Jumaa H, Müller MC, Hofmann WK, Hochhaus A, Ye BH, Agarwal A, Druker BJ, Shah NP, Melnick AM, Müschen M. BCL6-mediated repression of p53 is critical for leukemia stem cell survival in chronic myeloid leukemia. Journal Of Experimental Medicine 2011, 208: 2163-2174. PMID: 21911423, PMCID: PMC3201200, DOI: 10.1084/jem.20110304.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD34BenzamidesCell SurvivalDisease Models, AnimalDNA-Binding ProteinsForkhead Transcription FactorsHematopoietic Stem CellsHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMiceMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsPiperazinesProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-bcl-6PyrimidinesTumor Cells, CulturedTumor Suppressor Protein p53ConceptsChronic myeloid leukemiaLeukemia-initiating cellsCML-initiating cellsTyrosine kinase inhibitorsTKI treatmentCML patientsMyeloid leukemiaCML cellsInhibition of BCL6Leukemia stem cell survivalLeukemia initiationHuman CML cellsColony formationBCR-ABL1 tyrosine kinaseInitiation of leukemiaTransplant recipientsBlast crisis transformationRepression of p53Pharmacological inhibitionStem cell survivalCML samplesLeukemiaClinical validationKinase inhibitorsBCL6
2009
BCL6 Is Required for Leukemia-Initiation and Self-Renewal Signaling in Chronic Myeloid Leukemia.
Hurtz C, Duy C, Cerchietti L, Park E, Ci W, Swaminathan S, Kweon S, Klemm L, Kim Y, Martinelli G, Hofmann W, Ye B, Melnick A, Müschen M. BCL6 Is Required for Leukemia-Initiation and Self-Renewal Signaling in Chronic Myeloid Leukemia. Blood 2009, 114: 2167. DOI: 10.1182/blood.v114.22.2167.2167.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaHuman CML cellsCML cellsB cellsGC B cellsImatinib treatmentBCR-ABL1Large B-cell lymphomaInhibition of BCL6Chronic myeloid leukemiaBCL6 functionNovel therapeutic approachesB-cell lymphomaGerminal center B cellsTranscriptional repressor BCL6Myeloid progenitor cellsBCR-ABL1 kinaseImatinib resultsRole of BCL6Cell cycle arrestMyeloid leukemiaNovel peptide inhibitorTherapeutic approachesBone marrowProtein upregulation
2008
BCL6-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