2023
The Transcriptional Landscape of Ph+B-ALL Is Orchestrated By Long-Range Enhancer-Promoter Interactions and the Coordinated Action of Phosphorylation-Dependent and Phosphorylation-Independent Transcription Factors
Ng H, Robinson M, Malysheva V, Deniz O, Crump N, Cosgun K, Helian K, Spivakov M, Müschen M, Feldhahn N. The Transcriptional Landscape of Ph+B-ALL Is Orchestrated By Long-Range Enhancer-Promoter Interactions and the Coordinated Action of Phosphorylation-Dependent and Phosphorylation-Independent Transcription Factors. Blood 2023, 142: 2779. DOI: 10.1182/blood-2023-173435.Peer-Reviewed Original ResearchTranscription factorsTranscriptional programsEnhancer signatureGene expressionChromatin interactionsTranscriptional changesTyrosine kinaseAdditional transcription factorsMotif enrichment analysisPromoter-enhancer interactionsCis-regulatory elementsEnhancer-promoter interactionsPromoter capture HiNon-promoter regionsUnique transcriptional programGene expression changesCoordinated actionMurine B cell precursorsOncogenic tyrosine kinasesEnhancer usageActive chromatinActive genesEnhancer landscapeTranscriptional landscapeActive enhancers
2020
Signalling 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
2015
B-Lymphoid Transcription Factors Restrict Glycolytic Energy Supply for Oncogenic Signaling
Chan L, Chen Z, Braas D, Geng H, Hurtz C, Shojaee S, Cazzaniga V, Ng C, Ernst T, Hochhaus A, Kornblau S, Cazzaniga G, Liu G, Milne T, Koeffler H, Armstrong S, Dickins R, Yamamoto K, Graeber T, Muschen M. B-Lymphoid Transcription Factors Restrict Glycolytic Energy Supply for Oncogenic Signaling. Blood 2015, 126: 1255. DOI: 10.1182/blood.v126.23.1255.1255.Peer-Reviewed Original ResearchGlycolytic energy supplyLKB1-AMPKB cellsTranscription factorsGlucose uptakeMyeloid leukemiaMyeloid malignanciesDeletion of Lkb1Unknown functional significanceB-lineage leukemiasTranscriptional repressionTranscriptional programsMyeloid leukemia cellsLineage conversionHematopoietic progenitor cellsOncogenic signalingClinical characteristicsLineage shiftGenetic lesionsCell deathGlycolytic reserveOncogenic lesionsLeukemia casesInsulin receptorGlucocorticoid receptorSTAT5 antagonism of B cell superenhancer networks initiates progenitor B cell leukemia and predicts patient survival (HEM1P.222)
Farrar M, Katerndahl C, Heltemes Harris L, Willette M, Henzler C, Yang R, Silverstein K, Frietze S, Schjerven H, Ramsey L, Hubbard G, Muschen M, Kornblau S. STAT5 antagonism of B cell superenhancer networks initiates progenitor B cell leukemia and predicts patient survival (HEM1P.222). The Journal Of Immunology 2015, 194: 50.5-50.5. DOI: 10.4049/jimmunol.194.supp.50.5.Peer-Reviewed Original ResearchB cell developmentPatient outcomesB cellsB-cell acute lymphoblastic leukemiaProgenitor B cellsCell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaCell developmentDirect clinical relevanceB-cell leukemiaShort remissionsAggressive diseasePatient survivalLymphoblastic leukemiaTranscription factor STAT5Cell leukemiaClinical relevanceTranscriptional programsLeukemiaDegree of antagonismPre-BCRSurvivalSTAT5 activationMicroarray analysisSTAT5