2016
Oncogenic Feedback Activation Between BCL6 and MLL Promotes Malignant Transformation in MLL-RearrangedAcute Lymphoblastic Leukemia
Hurtz C, Chan L, Ballabio E, Willman C, Carroll W, Armstrong S, Ernst P, Melnick A, Milne T, Müschen M. Oncogenic Feedback Activation Between BCL6 and MLL Promotes Malignant Transformation in MLL-RearrangedAcute Lymphoblastic Leukemia. Blood 2016, 128: 907. DOI: 10.1182/blood.v128.22.907.907.Peer-Reviewed Original ResearchFunction of Bcl6Lymphoblastic leukemiaMLL-AF4Expression levelsPhiladelphia chromosome-positive acute lymphoblastic leukemiaBCL6 levelsPharmacological inhibitionDiffuse large B-cell lymphomaLarge B-cell lymphomaChemotherapy drugs vincristineTime of diagnosisWorse clinical outcomesBCL6 expressionHigh expression levelsRelapse-free survivalAcute lymphoblastic leukemiaChronic myeloid leukemiaB-cell lymphomaHigh-risk regimenMLL-ENLTransplant recipient miceB cell precursorsReporter mouse modelWestern blot analysisClinical outcomesFeedback Regulation of STAT5 Is Critical to Balance MYC and BCL6-Dependent Transcriptional Programs That Regulate Cell Size and Glucose Metabolism
Chen Z, Geng H, Klemm L, Chan L, Daniel B, Alexander W, Willman C, Müschen M. Feedback Regulation of STAT5 Is Critical to Balance MYC and BCL6-Dependent Transcriptional Programs That Regulate Cell Size and Glucose Metabolism. Blood 2016, 128: 4069. DOI: 10.1182/blood.v128.22.4069.4069.Peer-Reviewed Original ResearchBCR-ABL1Survival rateMedian expressionAdult B-lineageFree survival rateOverall survival rateWorse clinical outcomesGroup of patientsHigh expression levelsLeukemia cellsMRNA levelsNOD-SCID miceMYC expressionTyrosine kinase inhibitorsBCR-ABL1 tyrosine kinaseExpression levelsKinase inhibitory regionMedical Research CouncilAdvisory CommitteeInhibition of mTORGlucose consumptionCOG trialsLeukemia regressionTyrosine kinaseClinical outcomes
2015
Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia
Chen Z, Geng H, Lowell C, Weiss A, Hunger S, Melnick A, Muschen M. Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia. Blood 2015, 126: 3716. DOI: 10.1182/blood.v126.23.3716.3716.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsB cell receptorAcute lymphoblastic leukemiaPre-BCR signalingB cellsB cell selectionLymphoblastic leukemiaBCR-ABL1Autoreactive B cell receptorsCell deathPre-B-cell originAcute lymphoblastic leukemia cellsCurrent therapy approachesLeukemia cellsWorse clinical outcomesSelf-reactive B cellsNegative B cell selectionPotent tyrosine kinase inhibitorLymphoblastic leukemia cellsNovel small molecule inhibitorTypes of cancerUbiquitous self-antigenClinical outcomesIncremental increasePoor outcome
2014
Harnessing Negative B Cell Selection to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia
Chen Z, Shojaee S, Geng H, Lee J, Buchner M, Klemm L, Lowell C, Paietta E, Willman C, Carroll W, Melnick A, Jung J, Jumaa H, Coligan J, Bolland S, Mak T, Muschen M. Harnessing Negative B Cell Selection to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia. Blood 2014, 124: 792. DOI: 10.1182/blood.v124.21.792.792.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaTyrosine kinase inhibitorsB cell receptorInhibitory receptorsTherapeutic targetPre-BCR signalingLymphoblastic leukemiaXenograft cellsB cellsSurvival rateB-cell acute lymphoblastic leukemiaCell deathAuto-reactive clonesFree survival rateCell acute lymphoblastic leukemiaOverall survival rateWorse clinical outcomesLeukemia cellsNegative B cell selectionAdditional therapeutic targetsAvailable therapeutic interventionsG1cell cycle arrestPotent tyrosine kinase inhibitorNovel small molecule inhibitorColony formation capacity
2013
Identification Of BCL6 As a Therapeutic Target In MLL-Rearranged ALL
Hurtz C, Geng H, Ballabio E, Xiao G, Ng C, Masouleh B, Willman C, Armstrong S, Milne T, Melnick A, Muschen M. Identification Of BCL6 As a Therapeutic Target In MLL-Rearranged ALL. Blood 2013, 122: 72. DOI: 10.1182/blood.v122.21.72.72.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaFunction of Bcl6White blood countPoor clinical outcomeAcute lymphoblastic leukemiaMinimal residual diseaseClinical outcomesMLL-AF4Clinical trialsBCL6 levelsPositive minimal residual diseasePharmacological inhibitionHigher white blood countExpression levelsLarge B-cell lymphomaAberrant expressionChemotherapy drugs vincristineBCL6 protein levelsTime of diagnosisWorse clinical outcomesBCL6 expressionRelapse-free survivalProtein levelsPediatric clinical trialsB-cell lymphomaInhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia
Chen Z, Shojaee S, Geng H, Lee J, Buchner M, Klemm L, Lowell C, Paietta E, Willman C, Carroll W, Melnick A, Jung J, Jumaa H, Coligan J, Bolland S, Mak T, Muschen M. Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia. Blood 2013, 122: 229. DOI: 10.1182/blood.v122.21.229.229.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaB cell receptorTyrosine kinase inhibitorsInhibitory receptorsTherapeutic targetB cellsBCR-ABL1Survival rateB-cell lineage leukemiaCell deathAuto-reactive clonesFree survival rateLeukemia cellsOverall survival rateWorse clinical outcomesG0/G1 cell cycle arrestAdditional therapeutic targetsCycle arrestAvailable therapeutic interventionsG1cell cycle arrestPotential therapeutic targetG1 cell cycle arrestOncogenic tyrosine kinasesNovel small molecule inhibitorCellular senescence
2010
VPREB1 Deletions Occur Independent of Lambda-Light Chain Rearrangement and Predict Worse Outcome In Pediatric Acute Lymphoblastic Leukemia (ALL)
Miles R, Downie J, Jahromi M, Joshi D, Rodic V, Muschen M, Yang J, Evans W, Meeker N, Trede N, Frazer J, Barnette P, Schiffman J. VPREB1 Deletions Occur Independent of Lambda-Light Chain Rearrangement and Predict Worse Outcome In Pediatric Acute Lymphoblastic Leukemia (ALL). Blood 2010, 116: 273. DOI: 10.1182/blood.v116.21.273.273.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaLight chain rearrangementB cellsResearch HospitalWorse outcomesSt. Jude Children's Research HospitalCopy number alterationsPediatric acute lymphoblastic leukemiaB-cell developmental genesWorse clinical outcomesClinical risk stratificationSorted B cellsV-J junctionUnderstanding of leukemogenesisHomozygous deletionM2 marrowChain rearrangementClinical outcomesRisk stratificationLymphoblastic leukemiaEnhancer deletionBlood leukocytesHealthy volunteersHispanic ethnicityB cells results