2023
Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia
Ogana H, Hurwitz S, Hsieh C, Geng H, Müschen M, Bhojwani D, Wolf M, Larocque J, Lieber M, Kim Y. Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia. Frontiers In Cell And Developmental Biology 2023, 11: 1134121. PMID: 37082620, PMCID: PMC10111164, DOI: 10.3389/fcell.2023.1134121.Peer-Reviewed Original ResearchMature B cell lineB-cell acute lymphoblastic leukemiaB cell linesDNA double-strand break repairChromosome breaksDouble-strand break repairDNA-PKcs complexDNA-PK inhibitorGene expression analysisCell linesAcute lymphoblastic leukemiaKey endonucleaseDNA-PKcsBreak repairNonhomologous endExpression analysisLymphoblastic leukemiaTherapeutic strategiesRefractory B-cell acute lymphoblastic leukemiaHigh-risk prePharmacological inhibitionNovel therapeutic strategiesIndirect suppressionDirect inhibitionProliferation
2015
CD25 (IL2RA) Orchestrates Negative Feedback Control and Stabilizes Oncogenic Signaling Strength in Acute Lymphoblastic Leukemia
Lee J, Chen Z, Geng H, Xiao G, Eugene P, Parekh S, Kornblau S, Melnick A, Abbas A, Paietta E, Muschen M. CD25 (IL2RA) Orchestrates Negative Feedback Control and Stabilizes Oncogenic Signaling Strength in Acute Lymphoblastic Leukemia. Blood 2015, 126: 1434. DOI: 10.1182/blood.v126.23.1434.1434.Peer-Reviewed Original ResearchPre-BCR signalingPre-B cell receptorCytoplasmic tailOncogenic tyrosine kinasesB cell developmentTyrosine kinaseSerine/threonine protein kinaseCell developmentConstitutive membrane localizationCytoplasmic interaction partnersReceptor chainsEarly B cell developmentThreonine protein kinaseDownstream tyrosine kinasePre-B cell stageShort cytoplasmic tailNegative feedback controlComprehensive gene expression analysisDependent signal transductionTyrosine kinase BtkTyrosine kinase oncogenesGene expression analysisSerial transplantation experimentsB lineage cellsAbsence of CD25
2014
BACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia
Park E, Swaminathan S, Sadiyah M, Igarashi K, Melnick A, Muschen M. BACH2 promotes Lineage-Specific Fate Decisions in BCR-ABL1-Driven Leukemia. Blood 2014, 124: 513. DOI: 10.1182/blood.v124.21.513.513.Peer-Reviewed Original ResearchLymphoid blast crisisFate decisionsB-cell lineageCML-like diseaseCell lineagesTumor suppressorCML cellsBCR-ABL1Transcription factorsTransplant recipientsLineage-specific transcription factorsChronic phaseB-cell-specific transcription factorCell-specific transcription factorsBlast crisisPre-B cell receptor checkpointB-cell lineage leukemiaPrimary human CML cellsRole of Bach2Multi-lineage progenitor cellsEmpty vector controlGene expression analysisSelective proliferative advantagePotent tumor suppressorCML chronic phase
2012
Integrative Analysis of Ikaros-Dependent Changes of Transcriptional Regulation and Tyrosine Phosphorylation Events in Ph+ ALL
Geng H, Nahar R, Ramezani-Rad P, Chen Z, Tyner J, Chang B, Titz B, Buchner M, Hurtz C, Graeber T, Druker B, Paietta E, Melnick A, Willman C, Carroll W, Muschen M. Integrative Analysis of Ikaros-Dependent Changes of Transcriptional Regulation and Tyrosine Phosphorylation Events in Ph+ ALL. Blood 2012, 120: 528. DOI: 10.1182/blood.v120.21.528.528.Peer-Reviewed Original ResearchGene expression changesTyrosine phosphorylation eventsExpression changesTarget genesPhosphorylation eventsIkaros functionTyrosine phosphorylationClinical trial fundingTumor suppressorAbility of IkarosDependent survival signalsTyrosine kinase LckClinical trialsSet of genesBCL6 target genesComprehensive gene expression analysisChIP-seq dataIkaros transcription factorGene expression analysisRole of IkarosGene expression microarraysTrial fundingBristol-Myers SquibbClinical outcomesFurther biochemistry
2010
Mechanisms of Pre-B Cell Receptor-Inactivation In Acute Lymphoblastic Leukemia
Duy C, Nowak D, Klemm L, Nahar R, Ng C, Elliott E, Hofmann W, Heisterkamp N, Lowell C, Koeffler P, Muschen M. Mechanisms of Pre-B Cell Receptor-Inactivation In Acute Lymphoblastic Leukemia. Blood 2010, 116: 147. DOI: 10.1182/blood.v116.21.147.147.Peer-Reviewed Original ResearchPre-B cell receptorImmunoglobulin μ chainCell receptor functionCell receptor stimulationTyrosine kinasePAX5 fusion genesSystematic gene expression analysisΜ chainsSplice variantsCell receptorRapid cell cycle arrestExon 16Immunoglobulin gene rearrangementsReceptor functionReceptor signal transductionPre-B cell receptor functionGene rearrangementsGene expression analysisLeukemia cellsDominant-negative waySyk tyrosine kinaseCell cycle arrestPre B cellsSH2 domainMRNA splicing
2009
BCL6 Is Critical for the Development of a Diverse Primary B Cell Repertoire.
Duy C, Yu J, Swaminathan S, Nahar R, Kweon S, Polo J, Valls E, Klemm L, Cerchietti L, von Levetzow G, Herzog S, Jumaa H, de Alborán I, Melnick A, Ye B, Müschen M. BCL6 Is Critical for the Development of a Diverse Primary B Cell Repertoire. Blood 2009, 114: 91. DOI: 10.1182/blood.v114.22.91.91.Peer-Reviewed Original ResearchB cell developmentDNA damage stressTranscriptional repressionCell developmentPrimary B-cell repertoireBCL6 functionB cell precursorsDNA damage-induced apoptosisDNA damage response pathwayActive STAT5 mutantDNA damageEarly B cell developmentB cell repertoireNormal B cell developmentDamage response pathwayDamage-induced apoptosisEarly B cell differentiationGene expression patternsCell precursorsPre-B cell populationsSelf-renewal defectGene expression analysisDamage stressSimilar expression levelsEarly B-cell precursorsThe Pax5 Fusion Product Pax5-C20orf112 Causes Downregulation of Pre-B Cell Receptor Genes and Induces Differential Proliferation Patterns in B-Lymphoblastic Cell Lines.
Nowak D, Kawamata N, Niebuhr B, Nowak V, Mossner M, Nahar R, Thoennissen N, Iwanski G, Stocking C, Dugas M, Hofmann W, Müschen M, Koeffler P. The Pax5 Fusion Product Pax5-C20orf112 Causes Downregulation of Pre-B Cell Receptor Genes and Induces Differential Proliferation Patterns in B-Lymphoblastic Cell Lines. Blood 2009, 114: 1284. DOI: 10.1182/blood.v114.22.1284.1284.Peer-Reviewed Original ResearchPre-B cell receptor signalingPre-B cell receptorWild-type PAX5Cell receptor signalingImmunoglobulin heavy locusCandidate genesFusion productsCell linesFunctional pre-B cell receptorB-cell-specific transcription factor Pax5Spleen tyrosine kinaseGlobal gene expression analysisReceptor signalingPleckstrin homology domainRetroviral expression constructsB-cell linkerGroup of genesTranscription factor Pax5Promoter binding sitesAdaptor protein 1Receptor pathwayGene expression analysisEmpty vector controlGene expression microarraysCommon genomic lesions