2023
ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control
Gao Y, Zimmer J, Vasic R, Liu C, Gbyli R, Zheng S, Patel A, Liu W, Qi Z, Li Y, Nelakanti R, Song Y, Biancon G, Xiao A, Slavoff S, Kibbey R, Flavell R, Simon M, Tebaldi T, Li H, Halene S. ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control. Cell Reports 2023, 42: 113163. PMID: 37742191, PMCID: PMC10636609, DOI: 10.1016/j.celrep.2023.113163.Peer-Reviewed Original ResearchConceptsAlkB homolog 5Post-transcriptional regulatory mechanismsHematopoietic stemNumerous cellular processesProgenitor cell fitnessEnergy metabolismMitochondrial ATP productionMethyladenosine (m<sup>6</sup>A) RNA modificationTricarboxylic acid cycleCell energy metabolismHuman hematopoietic cellsMitochondrial energy productionCell fitnessCellular processesRNA modificationsRNA methylationRegulatory mechanismsEnzyme transcriptsATP productionHomolog 5Acid cycleΑ-ketoglutarateHematopoietic cellsMessenger RNAΑ-KGMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversity
2022
Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis
Öz H, Cheng E, Di Pietro C, Tebaldi T, Biancon G, Zeiss C, Zhang P, Huang P, Esquibies S, Britto C, Schupp J, Murray T, Halene S, Krause D, Egan M, Bruscia E. Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis. Cell Reports 2022, 41: 111797. PMID: 36516754, PMCID: PMC9833830, DOI: 10.1016/j.celrep.2022.111797.Peer-Reviewed Original ResearchConceptsC motif chemokine receptor 2Monocytes/macrophagesLung tissue damageCystic fibrosisTissue damageCF lungPulmonary neutrophilic inflammationPro-inflammatory environmentChemokine receptor 2CF lung diseaseNumber of monocytesSpecific therapeutic agentsGrowth factor βCF transmembrane conductance regulatorLung hyperinflammationLung neutrophiliaNeutrophilic inflammationNeutrophil inflammationInflammation contributesLung damageNeutrophil recruitmentLung diseaseLung tissueReceptor 2Therapeutic targetPre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal
Glasser E, Maji D, Biancon G, Puthenpeedikakkal AMK, Cavender CE, Tebaldi T, Jenkins JL, Mathews DH, Halene S, Kielkopf CL. Pre-mRNA splicing factor U2AF2 recognizes distinct conformations of nucleotide variants at the center of the pre-mRNA splice site signal. Nucleic Acids Research 2022, 50: 5299-5312. PMID: 35524551, PMCID: PMC9128377, DOI: 10.1093/nar/gkac287.Peer-Reviewed Original ResearchIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformationPrecision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original Research
2021
Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMice
2020
Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma
Ziccheddu B, Biancon G, Bagnoli F, De Philippis C, Maura F, Rustad EH, Dugo M, Devecchi A, De Cecco L, Sensi M, Terragna C, Martello M, Bagratuni T, Kastritis E, Dimopoulos MA, Cavo M, Carniti C, Montefusco V, Corradini P, Bolli N. Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma. Blood Advances 2020, 4: 830-844. PMID: 32126144, PMCID: PMC7065476, DOI: 10.1182/bloodadvances.2019000779.Peer-Reviewed Original ResearchConceptsChemotherapy resistanceMultiple myelomaProteasome inhibitorsDouble-refractory multiple myelomaHigh-risk featuresBulk tumor populationOverexpression of MCL1Whole-exome sequencingRefractory patientsImmunomodulatory agentsDisease progressionSame patientNovel treatmentsPatientsKaryotypic eventsEvolution of subclonesMyeloma cellsDrug resistanceMyelomaNovel targetIMiDsTumor populationGene mutationsNext-generation sequencingTP53 pathway
2019
Tyrosine kinase inhibition to improve anthracycline-based chemotherapy efficacy in T-cell lymphoma
Magni M, Biancon G, Rizzitano S, Cavanè A, Paolizzi C, Dugo M, Corradini P, Carniti C. Tyrosine kinase inhibition to improve anthracycline-based chemotherapy efficacy in T-cell lymphoma. British Journal Of Cancer 2019, 121: 567-577. PMID: 31474759, PMCID: PMC6889385, DOI: 10.1038/s41416-019-0557-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell CycleCell SurvivalCyclophosphamideDasatinibDoxorubicinDrug Administration ScheduleDrug SynergismEtoposideGene ExpressionGene Expression ProfilingHumansJurkat CellsLymphoma, T-CellMice, Inbred NODMice, SCIDPrednisoneProtein Kinase InhibitorsProtein-Tyrosine KinasesProto-Oncogene Proteins c-fynReceptors, Antigen, T-CellRhoA GTP-Binding ProteinTreatment OutcomeUp-RegulationVincristineConceptsT-cell lymphomaPeripheral T-cell lymphomaDrug combinationsTyrosine kinase inhibitor dasatinibVivo xenograft mouse modelMalignant T-cell linesXenograft mouse modelTyrosine kinase inhibitionTumor growth inhibitionKinase inhibitor dasatinibT cell receptorT cell linesT-cell receptor pathwayCell cycle distributionWestern blot analysisChemotherapy efficacyPreclinical modelsConclusionsOur dataMouse modelVivo effectsXenograft modelClinical testingTreatment resultsInhibitor dasatinibLymphomaFrom clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities?
Bewersdorf JP, Ardasheva A, Podoltsev NA, Singh A, Biancon G, Halene S, Zeidan AM. From clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities? Blood Reviews 2019, 37: 100587. PMID: 31400824, DOI: 10.1016/j.blre.2019.100587.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyeloid neoplasmsClonal hematopoiesisTherapy-related myeloid neoplasmsAnnual progression rateHealthy elderly individualsGenetic testing resultsCardiovascular mortalityHematologic disordersMyeloid leukemiaClinical significanceProgression ratePremalignant stateElderly individualsDiagnostic criteriaPreventive opportunitiesSolid tumorsClinical settingNatural historyFurther studiesPatientsSomatic mutationsRiskHematopoiesisCurrent understandingICUs
2018
Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA A Pilot Study
Biancon G, Gimondi S, Vendramin A, Carniti C, Corradini P. Noninvasive Molecular Monitoring in Multiple Myeloma Patients Using Cell-Free Tumor DNA A Pilot Study. Journal Of Molecular Diagnostics 2018, 20: 859-870. PMID: 30165206, DOI: 10.1016/j.jmoldx.2018.07.006.Peer-Reviewed Original ResearchConceptsTumor plasma cellsMultiple myelomaPlasma cellsResidual diseasePlasma samplesPilot studySecond-line therapyCell-free tumor DNA analysisMultiple myeloma patientsConventional laboratory parametersSerial plasma samplesMinimal residual diseaseBone marrow aspirateNumber of PCsTumor DNA analysisA Pilot StudyClonal IgH rearrangementsClonal IgH gene rearrangementsIgH gene rearrangementTumor clonotypesComplete responseLaboratory parametersMyeloma patientsCfDNA levelsTumor levelsAnalysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups
Bolli N, Biancon G, Moarii M, Gimondi S, Li Y, de Philippis C, Maura F, Sathiaseelan V, Tai YT, Mudie L, O’Meara S, Raine K, Teague JW, Butler AP, Carniti C, Gerstung M, Bagratuni T, Kastritis E, Dimopoulos M, Corradini P, Anderson KC, Moreau P, Minvielle S, Campbell PJ, Papaemmanuil E, Avet-Loiseau H, Munshi NC. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia 2018, 32: 2604-2616. PMID: 29789651, PMCID: PMC6092251, DOI: 10.1038/s41375-018-0037-9.Peer-Reviewed Original Research
2016
Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation
Gimondi S, Dugo M, Vendramin A, Bermema A, Biancon G, Cavané A, Corradini P, Carniti C. Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation. Experimental Hematology 2016, 44: 624-634.e1. PMID: 27013207, DOI: 10.1016/j.exphem.2016.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBiomarkersCluster AnalysisCombined Modality TherapyFemaleGene ExpressionGene Expression ProfilingGene Regulatory NetworksGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansLymphomaMaleMicroRNAsMiddle AgedPrognosisReproducibility of ResultsTime FactorsTransplantation, HomologousYoung AdultConceptsAllo-HSCTLymphoma patientsReal-time polymerase chain reactionAcute graftPolymerase chain reactionAllogeneic hematopoietic stem cell transplantationUnrelated hematopoietic stem cellHematopoietic stem cell transplantationHost disease (GVHD) resultsNon-aGVHD patientsStem cell transplantationChain reactionQuantitative real-time polymerase chain reactionRoutine clinical useCutaneous GVHDIntestinal GVHDHost diseaseSignificant morbidityUnrelated donorsCell transplantationPredictive biomarkersMicroRNA expression profileBlood samplingTherapeutic strategiesPatients