2018
Pre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia
Cosgun K, Hendriks R, Dickins R, Heisterkamp N, Muschen M. Pre-BCR Surrogate Light Chain Components VPREB1 and IGLL1 Function As Pre-BCR-Independent Tumor Suppressors in Acute Lymphoblastic Leukemia. Blood 2018, 132: 570. DOI: 10.1182/blood-2018-99-115522.Peer-Reviewed Original ResearchBCR-ABL1Transgenic miceSurrogate light chainTime of diagnosisTime of relapseDouble transgenic miceExerts tumor-suppressive effectsAcute lymphoblastic leukemiaB cell defectsDay of birthBCR-ABL1 tyrosine kinaseHigh surface levelsTumor-suppressive effectsPre-BCR expressionColony formation abilityPhosphorylation of BtkTumor suppressorBCR-ABL1 oncogeneEarly B cell developmentTumor suppressive functionLymphoblastic leukemiaCell cycle arrestFrequent lesionsSecondary lesionsSuppressive function
2016
Identification of the Energy Stress Sensor AMPK As Therapeutic Target in Acute Lymphoblastic Leukemia
Chan L, Lee J, Cosgun K, Geng H, Xiao G, Chen Z, Ernst T, Hochhaus A, Müschen M. Identification of the Energy Stress Sensor AMPK As Therapeutic Target in Acute Lymphoblastic Leukemia. Blood 2016, 128: 2771. DOI: 10.1182/blood.v128.22.2771.2771.Peer-Reviewed Original ResearchChronic myeloid leukemiaAcute lymphoblastic leukemiaMyeloid leukemiaTransplant recipient miceB-cell lineageLKB1/AMPKLymphoblastic leukemiaRecipient miceCML cellsTherapeutic targetLong-term disease-free survivalPhiladelphia chromosome-positive acute lymphoblastic leukemiaB-cell lineage leukemiaPatient-derived preDisease-free survivalInducible deletionNovel therapeutic targetGlycolytic activityBCR-ABL1 tyrosine kinaseNovel therapeutic avenuesATP levelsMitochondrial functionCell deathInitial remissionClinical characteristicsFeedback 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
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