2024
Tuning Responses to Polatuzumab Vedotin in B-cell Lymphoma.
Leveille E, Kothari S, Cosgun K, Mlynarczyk C, Müschen M. Tuning Responses to Polatuzumab Vedotin in B-cell Lymphoma. Cancer Discovery 2024, 14: 1577-1580. PMID: 39228298, DOI: 10.1158/2159-8290.cd-24-0644.Peer-Reviewed Original ResearchTherapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery
Chan A, Han L, Delaney C, Wang X, Mukhaleva E, Li M, Yang L, Pokharel S, Mattson N, Garcia M, Wang B, Xu X, Zhang L, Singh P, Elsayed Z, Chen R, Kuang B, Wang J, Yuan Y, Chen B, Chan L, Rosen S, Horne D, Müschen M, Chen J, Vaidehi N, Armstrong S, Su R, Chen C. Therapeutic targeting Tudor domains in leukemia via CRISPR-Scan Assisted Drug Discovery. Science Advances 2024, 10: eadk3127. PMID: 38394203, PMCID: PMC10889360, DOI: 10.1126/sciadv.adk3127.Peer-Reviewed Original ResearchConceptsTudor domainDrug discoveryRibosomal gene expressionMolecular dynamics simulationsDomain-focused CRISPR screeningDe novo drug discoveryCompound dockingAcetyltransferase complexCRISPR screensGenetic approachesLead inhibitorDynamics simulationsStructural genetics approachGene expressionH3K9 acetylationEpigenetic dysregulationSgf29Tile scansLeukemia progressionMultiple cancersDrug developmentDiscoveryH3K9DockingLeukemia
2023
Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression
Ecker V, Brandmeier L, Stumpf M, Giansanti P, Moreira A, Pfeuffer L, Fens M, Lu J, Kuster B, Engleitner T, Heidegger S, Rad R, Ringshausen I, Zenz T, Wendtner C, Müschen M, Jellusova J, Ruland J, Buchner M. Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression. Cell Reports 2023, 42: 113017. PMID: 37792532, DOI: 10.1016/j.celrep.2023.113017.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseChronic lymphocytic leukemiaCLL cellsMitochondrial reactive oxygen speciesChronic lymphocytic leukemia progressionApoptotic cell deathPoor clinical prognosisCLL cell survivalSmall molecule inhibitorsNegative feedback regulationProtein kinaseReactive oxygen speciesMAPK signalingMAPK activityPromising treatment conceptClinical prognosisClinical challengeLymphocytic leukemiaCell survivalAcute activationCell deathDNA damageDUSP6Treatment conceptFeedback regulationPD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma
Wartewig T, Daniels J, Schulz M, Hameister E, Joshi A, Park J, Morrish E, Venkatasubramani A, Cernilogar F, van Heijster F, Hundshammer C, Schneider H, Konstantinidis F, Gabler J, Klement C, Kurniawan H, Law C, Lee Y, Choi S, Guitart J, Forne I, Giustinani J, Müschen M, Jain S, Weinstock D, Rad R, Ortonne N, Schilling F, Schotta G, Imhof A, Brenner D, Choi J, Ruland J. PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma. Nature Cancer 2023, 4: 1508-1525. PMID: 37723306, PMCID: PMC10597841, DOI: 10.1038/s43018-023-00635-7.Peer-Reviewed Original ResearchConceptsPD-1T-NHLAP-1 activityT-cell non-Hodgkin lymphomaImmune checkpoint receptor PD-1Cell non-Hodgkin lymphomaCheckpoint receptor PD-1Receptor PD-1Non-Hodgkin lymphomaT-cell lymphomaT-cell malignanciesPrimary patient samplesTractable mouse modelAdvanced diseaseInferior prognosisProtein-1 transcription factorT cellsCell lymphomaMouse modelCell malignanciesATP citrate lyase activityACLY inhibitionPatient samplesTumor suppressive mechanismKey tumor suppressorEpigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis
Li M, Yang L, Chan A, Pokharel S, Liu Q, Mattson N, Xu X, Chang W, Miyashita K, Singh P, Zhang L, Li M, Wu J, Wang J, Chen B, Chan L, Lee J, Zhang X, Rosen S, Müschen M, Qi J, Chen J, Hiom K, Bishop A, Chen C. Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis. Advanced Science 2023, 10: 2206584. PMID: 37075745, PMCID: PMC10265057, DOI: 10.1002/advs.202206584.Peer-Reviewed Original ResearchConceptsProtein translation machineryHistone H4 acetylationOncogenic transcription factorNuA4 histoneChromatin remodelersGene bodiesEpigenetic networksTranslation machineryATPase componentEpigenetic controlTumor progressionCRISPR screensTranscription factorsH4 acetylationEpigenetic dysregulationRUVBL1Oncogenic signalingProtein synthesisPatient-derived samplesMYCPharmacological inhibitionEEF1A1 expressionMultiple cancersNovel opportunitiesDynamic interplayIsoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms
Taghi Khani A, Kumar A, Sanchez Ortiz A, Radecki K, Aramburo S, Lee S, Hu Z, Damirchi B, Lorenson M, Wu X, Gu Z, Stohl W, Sanz I, Meffre E, Müschen M, Forman S, Koff J, Walker A, Swaminathan S. Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms. Communications Biology 2023, 6: 295. PMID: 36941341, PMCID: PMC10027679, DOI: 10.1038/s42003-023-04667-8.Peer-Reviewed Original ResearchConceptsHuman B-cell malignanciesB-cell malignanciesB-cell neoplasmsB cellsPathogenic B cell subsetsPRL receptorsSLE-prone miceSystemic lupus erythematosusB cell numbersB cell subsetsB cell viabilityNormal B cellsExpression of Bcl2B cell survivalB-cell transformationLupus erythematosusLymphoproliferative diseaseAutocrine prolactinMouse modelPRLR isoformsMalignancyProlactinBCL2 expressionProlactin receptorIsoform-specific knockdown
2022
SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies
Leveille E, Chan LN, Mirza AS, Kume K, Müschen M. SYK and ZAP70 kinases in autoimmunity and lymphoid malignancies. Cellular Signalling 2022, 94: 110331. PMID: 35398488, DOI: 10.1016/j.cellsig.2022.110331.Peer-Reviewed Original ResearchConceptsChronic lymphocytic leukemiaB-cell malignanciesT cell receptorB cell receptorB-cell chronic lymphocytic leukemiaPathological B-cellsPoor clinical outcomeAcute lymphoblastic leukemiaExpression of SykT lymphocyte developmentClinical outcomesAggressive diseaseActivation of NFATAutoimmune diseasesLymphoblastic leukemiaT lymphocytesLymphocytic leukemiaCell lymphomaLymphoid malignanciesB cellsPI3K-pathwayOncogenic driversMalignancyNegative selectionPremalignant cells
2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCellsDevelopmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan WC, Meffre E, Martin T, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Molecular Cell 2021, 81: 2094-2111.e9. PMID: 33878293, PMCID: PMC8239336, DOI: 10.1016/j.molcel.2021.03.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19AutoimmunityB-LymphocytesCalciumCell DifferentiationCell Transformation, NeoplasticEnzyme ActivationHumansImmune ToleranceLymphoma, B-CellMiceModels, GeneticNeoplasm ProteinsNeoplasmsNFATC Transcription FactorsPhosphatidylinositol 3-KinasesProtein BindingReceptors, Antigen, B-CellSignal TransductionSyk KinaseZAP-70 Protein-Tyrosine KinasePON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis
Pan L, Hong C, Chan LN, Xiao G, Malvi P, Robinson ME, Geng H, Reddy ST, Lee J, Khairnar V, Cosgun KN, Xu L, Kume K, Sadras T, Wang S, Wajapeyee N, Müschen M. PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2016553118. PMID: 33531346, PMCID: PMC7896313, DOI: 10.1073/pnas.2016553118.Peer-Reviewed Original ResearchConceptsTransplant recipient miceDNA double-strand breaksNormal B cell developmentDouble-strand breaksB cell developmentGenetic deletionB cellsLymphoid transcription factorsGlucose transporter GLUT1Gatekeeper functionGlucose uptakeRecipient miceTranscription factorsSomatic recombinationSynthetic lethalityB-cell acute lymphoblastic leukemiaCell developmentMetabolic gatekeeperRefractory B-ALLDeficient murineCell acute lymphoblastic leukemiaPoor clinical outcomeCell typesAcute lymphoblastic leukemiaGlucose transport
2020
IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells
Lee J, Robinson ME, Ma N, Artadji D, Ahmed MA, Xiao G, Sadras T, Deb G, Winchester J, Cosgun KN, Geng H, Chan LN, Kume K, Miettinen TP, Zhang Y, Nix MA, Klemm L, Chen CW, Chen J, Khairnar V, Wiita AP, Thomas-Tikhonenko A, Farzan M, Jung JU, Weinstock DM, Manalis SR, Diamond MS, Vaidehi N, Müschen M. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells. Nature 2020, 588: 491-497. PMID: 33149299, PMCID: PMC8087162, DOI: 10.1038/s41586-020-2884-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19B-LymphocytesCell Transformation, NeoplasticFemaleGerminal CenterHumansIntegrinsMembrane MicrodomainsMembrane ProteinsMiceMice, Inbred C57BLMice, Inbred NODModels, MolecularPhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphorylationReceptors, Antigen, B-CellRNA-Binding ProteinsSignal TransductionConceptsPI3KCell leukemiaAntiviral effector functionsAntigen-specific antibodiesInterferon-induced transmembrane proteinsIFITM3 functionDevelopment of leukemiaCell surfacePoor outcomeOncogenic PI3KClinical cohortEffector functionsGerminal centersMouse modelB cellsExpression of IFITM3Malignant transformationAccumulation of PIP3PI3K signalsCell receptorNormal numbersLeukemiaDefective expressionEndosomal proteinIFITM3Signalling input from divergent pathways subverts B cell transformation
Chan LN, Murakami MA, Robinson ME, Caeser R, Sadras T, Lee J, Cosgun KN, Kume K, Khairnar V, Xiao G, Ahmed MA, Aghania E, Deb G, Hurtz C, Shojaee S, Hong C, Pölönen P, Nix MA, Chen Z, Chen CW, Chen J, Vogt A, Heinäniemi M, Lohi O, Wiita AP, Izraeli S, Geng H, Weinstock DM, Müschen M. Signalling input from divergent pathways subverts B cell transformation. Nature 2020, 583: 845-851. PMID: 32699415, PMCID: PMC7394729, DOI: 10.1038/s41586-020-2513-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell Line, TumorCell Transformation, NeoplasticEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansLeukemia, B-CellMiceProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycSignal TransductionSTAT5 Transcription FactorConceptsPre-B cell receptorPrincipal oncogenic driverDivergent pathwaysSignal transduction proteinsPro-B cell stageSingle-cell mutationTranscription factor MYCOncogenic driversDivergent signaling pathwaysSingle oncogenic pathwayCentral oncogenic driverMore mature cellsGenetic reactivationTranscriptional programsB-cell transformationProtein kinasePathway componentsERK activationIndividual mutationsOncogenic STAT5Signaling pathwaysCell transformationCytokine receptorsGenetic lesionsDivergent circuits
2019
Rationale for targeting BCL6 in MLL-rearranged acute lymphoblastic leukemia
Hurtz C, Chan LN, Geng H, Ballabio E, Xiao G, Deb G, Khoury H, Chen CW, Armstrong SA, Chen J, Ernst P, Melnick A, Milne T, Müschen M. Rationale for targeting BCL6 in MLL-rearranged acute lymphoblastic leukemia. Genes & Development 2019, 33: 1265-1279. PMID: 31395741, PMCID: PMC6719625, DOI: 10.1101/gad.327593.119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell SurvivalCells, CulturedGene DeletionGene Expression Regulation, LeukemicGene TargetingHumansMiceMyeloid-Lymphoid Leukemia ProteinOncogene Proteins, FusionPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisPromoter Regions, GeneticProto-Oncogene Proteins c-bcl-6ConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaPharmacological inhibitionGroup of patientsBCL6 expressionBone marrow biopsyBH3 mimetic ABT-199Transplant recipient miceMLL fusionsB-cell transformationMarrow biopsyTreatment of MLLDismal outcomeRecipient miceNormal B cell developmentImmunohistochemical stainingTranscriptional activationB cell developmentMalignant transformationDrug resistanceGenetic deletionPatient samplesExpression of BimMLL-ENL fusionMetabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation
Müschen M. Metabolic gatekeepers to safeguard against autoimmunity and oncogenic B cell transformation. Nature Reviews Immunology 2019, 19: 337-348. PMID: 30890785, DOI: 10.1038/s41577-019-0154-3.Peer-Reviewed Original ResearchConceptsB cell receptorAutoreactive B cell receptorsLineage-determining transcription factorsMetabolic gatekeeperMitochondrial ATP productionB-cell transformationTranscription factorsEnergy stressPhosphate pathway activityATP productionCell transformationSmall cytoplasmic volumeCell deathPathway activityB cellsEnergy metabolismCell proliferationCytoplasmic volumeCell receptorGlucose uptakeOncogeneB cell proliferationCellsMetabolic demandsAdditional glucoseHistone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
Huang H, Weng H, Zhou K, Wu T, Zhao BS, Sun M, Chen Z, Deng X, Xiao G, Auer F, Klemm L, Wu H, Zuo Z, Qin X, Dong Y, Zhou Y, Qin H, Tao S, Du J, Liu J, Lu Z, Yin H, Mesquita A, Yuan CL, Hu YC, Sun W, Su R, Dong L, Shen C, Li C, Qing Y, Jiang X, Wu X, Sun M, Guan JL, Qu L, Wei M, Müschen M, Huang G, He C, Yang J, Chen J. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally. Nature 2019, 567: 414-419. PMID: 30867593, PMCID: PMC6438714, DOI: 10.1038/s41586-019-1016-7.Peer-Reviewed Original ResearchConceptsM6A methyltransferase complexHistone H3 trimethylationH3 trimethylationHistone modificationsImportant post-transcriptional mechanismMouse embryonic stem cellsGene expression regulationRNA polymerase IIPrevalent internal modificationPost-transcriptional mechanismsEmbryonic stem cellsN6-methyladenosine (m<sup>6</sup>A) mRNA modificationM6A depositionTranscription elongationNascent RNAMethyltransferase complexPolymerase IIExpression regulationGene expression1RNA methylationMRNA modificationMETTL14 knockdownH3K36me3M6A modificationCell stemness
2018
B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies
Xiao G, Chan LN, Klemm L, Braas D, Chen Z, Geng H, Zhang QC, Aghajanirefah A, Cosgun KN, Sadras T, Lee J, Mirzapoiazova T, Salgia R, Ernst T, Hochhaus A, Jumaa H, Jiang X, Weinstock DM, Graeber TG, Müschen M. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies. Cell 2018, 173: 470-484.e18. PMID: 29551267, PMCID: PMC6284818, DOI: 10.1016/j.cell.2018.02.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCarbonCell Line, TumorCell SurvivalGlucoseGlucosephosphate DehydrogenaseGlycolysisHumansIkaros Transcription FactorMiceMice, Inbred C57BLMice, Inbred NODOxidative StressPAX5 Transcription FactorPentose Phosphate PathwayPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Phosphatase 2Proto-Oncogene Proteins c-bcl-2Transcription, GeneticConceptsPentose phosphate pathwayCarbon utilizationSerine/threonine protein phosphatase 2AB-cell transcription factor PAX5Transcription factor Pax5Favor of glycolysisSmall molecule inhibitionPhosphatase 2ATranscriptional repressionRedox homeostasisOncogenic transformationTumor suppressorMolecule inhibitionPP2AGenetic studiesPhosphate pathwayB cell activationEssential roleB-cell malignanciesCell malignanciesB cellsAntioxidant protectionOxidative stressB-cell tumorsCell activationAutoimmunity checkpoints as therapeutic targets in B cell malignancies
Müschen M. Autoimmunity checkpoints as therapeutic targets in B cell malignancies. Nature Reviews Cancer 2018, 18: 103-116. PMID: 29302068, DOI: 10.1038/nrc.2017.111.Peer-Reviewed Original Research
2017
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Takao S, Chien W, Madan V, Lin D, Ding L, Sun Q, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang Y, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler H. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia 2017, 32: 616-625. PMID: 28904384, DOI: 10.1038/leu.2017.281.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAminopyridinesAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalCytokinesDisease Models, AnimalFemaleHumansMaleMiceNADNicotinamide PhosphoribosyltransferaseP21-Activated KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSignal TransductionXenograft Model Antitumor AssaysConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaP21-activated kinase 4Nicotinamide phosphoribosyltransferaseLymphoblastic leukemiaNAMPT inhibitionPatient-derived xenograft murine modelsPrognosis of patientsNicotinamide adenine dinucleotideNovel therapeutic strategiesNicotinic acid supplementationNovel dual inhibitorXenograft murine modelCell growth inhibitionAcid supplementationMurine modelTherapeutic strategiesRate-limiting enzymeCytogenetic abnormalitiesVivo efficacyPatientsNAMPT inhibitorsInhibitory effectDual inhibitorKinase 4Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival
Katerndahl CDS, Heltemes-Harris LM, Willette MJL, Henzler CM, Frietze S, Yang R, Schjerven H, Silverstein KAT, Ramsey LB, Hubbard G, Wells AD, Kuiper RP, Scheijen B, van Leeuwen FN, Müschen M, Kornblau SM, Farrar MA. Antagonism of B cell enhancer networks by STAT5 drives leukemia and poor patient survival. Nature Immunology 2017, 18: 694-704. PMID: 28369050, PMCID: PMC5540372, DOI: 10.1038/ni.3716.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAgammaglobulinaemia Tyrosine KinaseAnimalsB-LymphocytesChromatin ImmunoprecipitationFlow CytometryGene Expression Regulation, NeoplasticHumansIkaros Transcription FactorInterferon Regulatory FactorsMiceMultiplex Polymerase Chain ReactionNF-kappa B p50 SubunitPAX5 Transcription FactorPre-B Cell ReceptorsPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProtein Kinase C betaProtein-Tyrosine KinasesProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionSignal TransductionSTAT5 Transcription FactorSurvival RateTrans-ActivatorsMetabolic gatekeeper function of B-lymphoid transcription factors
Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature 2017, 542: 479-483. PMID: 28192788, PMCID: PMC5621518, DOI: 10.1038/nature21076.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsB-LymphocytesCarcinogenesisCarrier ProteinsCell DeathChromatin ImmunoprecipitationCitric Acid CycleDisease Models, AnimalEnergy MetabolismFemaleGene Expression Regulation, NeoplasticGlucocorticoidsGlucoseHumansIkaros Transcription FactorMiceMice, TransgenicPAX5 Transcription FactorPrecursor B-Cell Lymphoblastic Leukemia-LymphomaProtein Serine-Threonine KinasesPyruvic AcidReceptor, Cannabinoid, CB2Receptors, GlucocorticoidSequence Analysis, RNATranscription Factors