2015
Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia
Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen WY, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH, Müschen M. Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia. Cancer Cell 2015, 27: 409-425. PMID: 25759025, PMCID: PMC4618684, DOI: 10.1016/j.ccell.2015.02.003.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsClinical Trials as TopicDNA-Binding ProteinsGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMolecular Sequence DataPhosphatidylinositol 3-KinasePre-B-Cell Leukemia Transcription Factor 1Precursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-6Signal TransductionSrc-Family KinasesSyk KinaseUp-RegulationConceptsDistinct subtypesPre-BCR signalingPatient-derived preVivo treatment studiesTreatment of patientsAcute lymphoblastic leukemiaTyrosine kinase inhibitorsPre-B cell receptor signalingCell receptor signalingLymphoblastic leukemiaClinical trialsTreatment studiesPre-BCR functionReceptor signalingKinase inhibitorsDistinct subsetsBCL6 expressionInduced activationFeedback activationSubtypesTyrosine kinaseBCL6SignalingActivationTranscriptional level
2014
Self-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
2009
BCL6-Dependent Negative Regulation of Cell Cycle Checkpoint Regulators Enables Drug-Resistance in Ph+ Acute Lymphoblastic Leukemia.
Duy C, Cerchietti L, Yu J, Ci W, Swaminathan S, Nahar R, Kweon S, Klemm L, Ye B, Melnick A, Müschen M. BCL6-Dependent Negative Regulation of Cell Cycle Checkpoint Regulators Enables Drug-Resistance in Ph+ Acute Lymphoblastic Leukemia. Blood 2009, 114: 765. DOI: 10.1182/blood.v114.22.765.765.Peer-Reviewed Original ResearchB-cell lymphomaTyrosine kinase inhibitorsCell lymphomaBCR-ABL1TKI treatmentCheckpoint regulatorsBCR-ABL1 tyrosine kinase inhibitorsCell cycle checkpoint regulatorsNOD/SCID miceFunction of Bcl6Leukemia cell injectionTreatment of patientsAcute lymphoblastic leukemiaCombination of imatinibCombination of nilotinibKinase inhibitor nilotinibB-cell lymphoma cellsPeptide inhibitionPotential therapeutic usefulnessFunction experimentsB cell precursorsCell lymphoma cellsTranscriptional suppressionQuantitative RT-PCRMedian survivalThe B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia.
Klemm L, Duy C, Iacobucci I, von Levetzow G, Feldhahn N, Kim Y, Hofmann W, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber M, Casellas R, Müschen M. The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia. Blood 2009, 114: 3274. DOI: 10.1182/blood.v114.22.3274.3274.Peer-Reviewed Original ResearchBCR-ABL1 mutationsChronic myeloid leukemiaLymphoid blast crisisB-lymphoid blast crisisBCR-ABL1 kinase domainImatinib resistanceCML cellsBCR-ABL1Gene copy number alterationsDrug resistanceLeukemia cellsOverall survivalMyeloid leukemiaBlast crisisFive-year overall survivalCopy number alterationsNOD/SCID miceMedian overall survivalTreatment of patientsExpression of CD19Imatinib-resistant clonesMechanisms of progressionKinase inhibitor imatinibPresence of imatinibConcentrations of imatinib