2015
Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia
Swaminathan S, Klemm L, Park E, Papaemmanuil E, Ford A, Kweon SM, Trageser D, Hasselfeld B, Henke N, Mooster J, Geng H, Schwarz K, Kogan SC, Casellas R, Schatz DG, Lieber MR, Greaves MF, Müschen M. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia. Nature Immunology 2015, 16: 766-774. PMID: 25985233, PMCID: PMC4475638, DOI: 10.1038/ni.3160.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAnimalsAntibody DiversityB-LymphocytesChildChild, PreschoolClonal EvolutionCytidine DeaminaseDNA-Binding ProteinsFemaleFlow CytometryHomeodomain ProteinsHumansImmunoblottingInfantMaleMice, Inbred NODMice, KnockoutMice, SCIDMice, TransgenicMicroscopy, FluorescencePrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor Cells, B-LymphoidReverse Transcriptase Polymerase Chain ReactionTumor Cells, Cultured
2013
AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine
Tsai CT, Yang PM, Chern TR, Chuang SH, Lin JH, Klemm L, Müschen M, Chen CC. AID downregulation is a novel function of the DNMT inhibitor 5-aza-deoxycytidine. Oncotarget 2013, 5: 211-223. PMID: 24457556, PMCID: PMC3960202, DOI: 10.18632/oncotarget.1319.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseClass switch recombinationTumor suppressor geneHematopoietic cancer cellsAID expressionSomatic hypermutationNovel biological functionDNMT inhibitor 5Cancer cellsHost genesProteasomal degradationDNMT inhibitorsNovel functionBiological functionsInhibitor 5Suppressor geneSwitch recombinationImmunoglobulin genesCancer progressionCytidine deaminaseGenesDNMT1ZEBMolecular dockingActive siteBoth CpG Methylation and Activation-Induced Deaminase Are Required for the Fragility of the Human bcl-2 Major Breakpoint Region: Implications for the Timing of the Breaks in the t(14;18) Translocation
Cui X, Lu Z, Kurosawa A, Klemm L, Bagshaw AT, Tsai AG, Gemmell N, Müschen M, Adachi N, Hsieh CL, Lieber MR. Both CpG Methylation and Activation-Induced Deaminase Are Required for the Fragility of the Human bcl-2 Major Breakpoint Region: Implications for the Timing of the Breaks in the t(14;18) Translocation. Molecular And Cellular Biology 2013, 33: 947-957. PMID: 23263985, PMCID: PMC3623081, DOI: 10.1128/mcb.01436-12.Peer-Reviewed Original ResearchB-LymphocytesCell LineChromosome BreakpointsChromosomes, Human, Pair 14Chromosomes, Human, Pair 18CpG IslandsCytidine DeaminaseDNADNA MethylationDNA-Binding ProteinsEndonucleasesGene Knockout TechniquesGenes, bcl-2Homeodomain ProteinsHumansNuclear ProteinsProto-Oncogene Proteins c-bcl-2Translocation, Genetic
2009
The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug Resistance in Chronic Myeloid Leukemia
Klemm L, Duy C, Iacobucci I, Kuchen S, von Levetzow G, Feldhahn N, Henke N, Li Z, Hoffmann TK, Kim YM, Hofmann WK, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber MR, Casellas R, Müschen M. The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug Resistance in Chronic Myeloid Leukemia. Cancer Cell 2009, 16: 232-245. PMID: 19732723, PMCID: PMC2931825, DOI: 10.1016/j.ccr.2009.07.030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBenzamidesBlast CrisisCell Line, TumorCytidine DeaminaseDrug Resistance, NeoplasmFusion Proteins, bcr-ablGreen Fluorescent ProteinsHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLuciferases, RenillaMiceMice, Inbred BALB CMice, KnockoutMice, SCIDMice, TransgenicMutationPiperazinesPyrimidinesXenograft Model Antitumor AssaysConceptsLymphoid blast crisisChronic myeloid leukemiaB-lymphoid blast crisisBCR-ABL1 mutationsDrug resistanceMyeloid leukemiaBlast crisisCML cellsMechanisms of progressionImatinib resistanceClinical significanceBCR-ABL1Causative roleDNA repair genesLeukemia cellsRepair genesLeukemiaTumor suppressorAID expressionOverall genetic instabilityProgressionCellsGenetic instabilityImatinibMutations