2021
Targeting the T-Cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune-Modulatory Signaling PathwaysTargeting Peripheral T-Cell Lymphoma Epigenome
Scotto L, Kinahan C, Douglass E, Deng C, Safari M, Casadei B, Marchi E, Lue JK, Montanari F, Falchi L, Qiao C, Renu N, Bates SE, Califano A, O'Connor OA. Targeting the T-Cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune-Modulatory Signaling PathwaysTargeting Peripheral T-Cell Lymphoma Epigenome. Molecular Cancer Therapeutics 2021, 20: 1422-1430. PMID: 34108263, PMCID: PMC8941846, DOI: 10.1158/1535-7163.mct-20-0377.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmAntimetabolites, AntineoplasticApoptosisAzacitidineBiomarkers, TumorCell ProliferationDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationEpigenesis, GeneticEpigenomeGene Expression ProfilingGene Expression Regulation, NeoplasticHistone Deacetylase InhibitorsHumansImmunityLymphoma, T-CellMaleTestisTumor Cells, CulturedConceptsEpigenetic geneHistone deacetylaseSuppression of genesHDAC inhibitorsDNA methyltransferase inhibitorTranscriptional inductionDNA methylationMaster regulatorDNMT inhibitorsEpigenetic diseasePeripheral T-cell lymphomaGene expressionMethyltransferase inhibitorMechanistic basisCell deathGenesCancer-testis antigensTestis antigensEpigenomeMutationsCholesterol metabolismInhibitorsInductionMatrisomeTh1-like phenotypeCombined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study
Falchi L, Ma H, Klein S, Lue JK, Montanari F, Marchi E, Deng C, Kim HA, Rada A, Jacob AT, Kinahan C, Francescone MM, Soderquist CR, Park DC, Bhagat G, Nandakumar R, Menezes D, Scotto L, Sokol L, Shustov AR, O’Connor O. Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study. Blood 2021, 137: 2161-2170. PMID: 33171487, DOI: 10.1182/blood.2020009004.Peer-Reviewed Original ResearchConceptsPeripheral T-cell lymphomaOverall response rateMedian progression-free survivalProgression-free survivalT-cell lymphomaOverall survivalR Peripheral T Cell LymphomaResponse rateFollicular helper cell phenotypeMulticenter phase 2 studyHigher overall response rateFrequent grade 3Complete response rateComplete remission ratePhase 2 studyPhase 1 trialDuration of responseHelper cell phenotypeLonger median survivalHistone deacetylase inhibitorsPTCL patientsR diseaseTreatment-naïveMedian survivalRemission rate
2020
Generation of pralatrexate resistant T‐cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers
Scotto L, Kinahan C, Casadei B, Mangone M, Douglass E, Murty VV, Marchi E, Ma H, George C, Montanari F, Califano A, O'Connor OA. Generation of pralatrexate resistant T‐cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers. Genes Chromosomes And Cancer 2020, 59: 639-651. PMID: 32614991, PMCID: PMC7540375, DOI: 10.1002/gcc.22884.Peer-Reviewed Original ResearchConceptsDihydrofolate reductaseResistant cell linesGene expression profilesCell linesT-cell lymphoma lineAntifolate pharmacologyEpigenetic modifiersExpression analysisGene expressionExpression profilesMechanistic basisT-cell selectivityParental H9 cellsIncreases expressionT-cell lymphomaSTAT5 phosphorylationMolecular targetsGene amplificationConcentration-dependent fashionLymphoma linesH9 cellsDrug resistancePutative mechanismsCellsPutative biomarkers