2009
Activation-Induced Cytidine Deaminase Accelerates Clonal Evolution of BCR-ABL1-Driven B Cell Lineage Acute Lymphoblastic Leukemia.
Gruber T, Chang M, Sposto R, Müschen M. Activation-Induced Cytidine Deaminase Accelerates Clonal Evolution of BCR-ABL1-Driven B Cell Lineage Acute Lymphoblastic Leukemia. Blood 2009, 114: 181. DOI: 10.1182/blood.v114.22.181.181.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAberrant AID expressionBCR-ABL1Lymphoblastic leukemiaB cellsBCR-ABL1 kinase domain mutationsB-cell lineage acute lymphoblastic leukemiaClonal evolutionTumor suppressor geneAberrant somatic hypermutationAID expressionB-cell lymphomaKinase domain mutationsGerminal center B cellsBone marrow cellsSuppressor geneBCR-ABL1 kinaseGC B cellsHazard ratioMedian survivalGenetic instabilityImatinib treatmentSomatic hypermutationB-cell lymphomagenesisCell lymphoma
2008
Lymphoid Blast Crisis Transformation and Development of Drug- Resistance in Chronic Myeloid Leukemia Are Driven by Aberrant Somatic Hypermutation
Klemm L, Duy C, Feldhahn N, Groffen J, Kim Y, Hofmann W, Jumaa H, Lieber M, Casellas R, Muschen M. Lymphoid Blast Crisis Transformation and Development of Drug- Resistance in Chronic Myeloid Leukemia Are Driven by Aberrant Somatic Hypermutation. Blood 2008, 112: 571. DOI: 10.1182/blood.v112.11.571.571.Peer-Reviewed Original ResearchChronic phase chronic myeloid leukemiaPhase chronic myeloid leukemiaChronic myeloid leukemiaLymphoid blast crisisGerminal center B cellsAberrant somatic hypermutationSomatic hypermutationBCR-ABL1 kinase domainKinase domainEctopic expressionB cell lineage commitmentB-cell-specific transcription factor Pax5Lineage-specific activationCML cellsAID protein levelsImatinib resistanceAberrant activationB cellsTranscription factor Pax5AID expressionBCR-ABL1Cell lineage commitmentCytidine deaminase AIDDownstream regulatory elementsB-cell-specific activation
2007
PAX5-Mediated Lineage Conversion and Expression of AID Accelerates Clonal Evolution and Initiates Darwinian Selection of BCR-ABL1-Mutants in Chronic Myeloid Leukemia.
Klemm L, Feldhahn N, Hoffmann T, Hofmann W, Jumaa H, Muschen M. PAX5-Mediated Lineage Conversion and Expression of AID Accelerates Clonal Evolution and Initiates Darwinian Selection of BCR-ABL1-Mutants in Chronic Myeloid Leukemia. Blood 2007, 110: 1005. DOI: 10.1182/blood.v110.11.1005.1005.Peer-Reviewed Original ResearchLineage conversionCell lineagesDarwinian selectionKinase domainB-cell lineageCell linesSequence analysisEnzyme AIDCML cell linesRetroviral expression constructsTranscription factor Pax5CML linesAID expressionDrug-resistant cellsCell lineage conversionTumor suppressor gene CDKN2ABlast crisis chronic myeloid leukemiaBCR-ABL1 kinaseActivation-induced cytidine deaminase acts as a mutator in BCR-ABL1–transformed acute lymphoblastic leukemia cells
Feldhahn N, Henke N, Melchior K, Duy C, Soh BN, Klein F, von Levetzow G, Giebel B, Li A, Hofmann WK, Jumaa H, Müschen M. Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1–transformed acute lymphoblastic leukemia cells. Journal Of Experimental Medicine 2007, 204: 1157-1166. PMID: 17485517, PMCID: PMC2118573, DOI: 10.1084/jem.20062662.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBlotting, WesternB-LymphocytesCytidine DeaminaseDNA Mutational AnalysisDNA-Binding ProteinsFlow CytometryFusion Proteins, bcr-ablGene Expression Regulation, NeoplasticGenes, mycHumansImmunoglobulin Variable RegionMolecular Sequence DataMutationOligonucleotide Array Sequence AnalysisOligonucleotidesPhiladelphia ChromosomePrecursor Cell Lymphoblastic Leukemia-LymphomaProtein-Tyrosine KinasesProto-Oncogene Proteins c-bcl-6Reverse Transcriptase Polymerase Chain ReactionRNA InterferenceSequence AlignmentConceptsAcute lymphoblastic leukemiaBCR-ABL1BCR-ABL1 kinaseUnfavorable prognosisActivation-induced cytidine deaminaseAcute lymphoblastic leukemia cellsAID expressionAberrant AID expressionBCR-ABL1 kinase activityIgH V region genesTumor suppressor gene CDKN2BGerminal center B cellsLymphoblastic leukemia cellsB cell precursorsImmunoglobulin heavy chain variable region genesLymphoblastic leukemiaLeukemia subsetsB cellsDNA single-strand breaksPH casesPhiladelphia chromosomeHeavy chain variable region genesAberrant expressionCell precursorsChain variable region genes