Featured Publications
Precision 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 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 ResearchMeSH KeywordsEnzyme InhibitorsHumansIsocitrate DehydrogenaseLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesPoly(ADP-ribose) Polymerase InhibitorsRecurrenceConceptsAcute 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 transformationA highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies
Song Y, Rongvaux A, Taylor A, Jiang T, Tebaldi T, Balasubramanian K, Bagale A, Terzi YK, Gbyli R, Wang X, Fu X, Gao Y, Zhao J, Podoltsev N, Xu M, Neparidze N, Wong E, Torres R, Bruscia EM, Kluger Y, Manz MG, Flavell RA, Halene S. A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies. Nature Communications 2019, 10: 366. PMID: 30664659, PMCID: PMC6341122, DOI: 10.1038/s41467-018-08166-x.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsMyelodysplastic syndromeXenotransplantation modelDysplastic morphologyImmunodeficient murine hostsPre-clinical studiesMDS stem cellsMDS subtypesComprehensive preclinical studiesPreclinical studiesTherapeutic efficacyMurine hostSerial transplantationDrug mechanismsMDS researchStem cell propagationStem cellsDifferentiation potentialHematopoietic stem cell nicheGenetic complexityNovel avenuesStem cell nicheCell propagationDisease representationsImmunodeficientHow do messenger RNA splicing alterations drive myelodysplasia?
Joshi P, Halene S, Abdel-Wahab O. How do messenger RNA splicing alterations drive myelodysplasia? Blood 2017, 129: 2465-2470. PMID: 28348147, PMCID: PMC5418633, DOI: 10.1182/blood-2017-02-692715.Commentaries, Editorials and LettersEpigenesis, GeneticHumansMyelodysplastic SyndromesPhosphoproteinsRNA SplicingRNA Splicing FactorsRNA, Messenger
2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsHistone Deacetylase InhibitorsHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacyClassification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS)
Stahl M, Bewersdorf J, Xie Z, Porta M, Komrokji R, Xu M, Abdel-Wahab O, Taylor J, Steensma D, Starczynowski D, Sekeres M, Sanz G, Sallman D, Roboz G, Platzbecker U, Patnaik M, Padron E, Odenike O, Nimer S, Nazha A, Majeti R, Loghavi S, Little R, List A, Kim T, Hourigan C, Hasserjian R, Halene S, Griffiths E, Gore S, Greenberg P, Figueroa M, Fenaux P, Efficace F, DeZern A, Daver N, Churpek J, Carraway H, Buckstein R, Brunner A, Boultwood J, Borate U, Bejar R, Bennett J, Wei A, Santini V, Savona M, Zeidan A. Classification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS). Blood Reviews 2023, 62: 101128. PMID: 37704469, DOI: 10.1016/j.blre.2023.101128.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational consensus classificationResponse assessmentWorld Health Organization classificationPatient-centered careRisk assessment toolClinical outcomesRisk stratificationOrganization classificationCentered careTherapeutic benefitTherapeutic outcomesConsensus classificationResponse criteriaInternational ConsortiumNeoplasmsLife assessmentAssessment toolOutcomesReportAssessmentPrognosticationCareAn agenda to advance research in myelodysplastic syndromes: a TOP 10 priority list from the first international workshop in MDS
Stahl M, Abdel-Wahab O, Wei AH, Savona MR, Xu ML, Xie Z, Taylor J, Starczynowski D, Sanz GF, Sallman DA, Santini V, Roboz GJ, Patnaik MM, Padron E, Odenike O, Nazha A, Nimer SD, Majeti R, Little RF, Gore S, List AF, Kutchroo V, Komrokji RS, Kim TK, Kim N, Hourigan CS, Hasserjian RP, Halene S, Griffiths EA, Greenberg PL, Figueroa M, Fenaux P, Efficace F, DeZern AE, Della Porta MG, Daver NG, Churpek JE, Carraway HE, Brunner AM, Borate U, Bennett JM, Bejar R, Boultwood J, Loghavi S, Bewersdorf JP, Platzbecker U, Steensma DP, Sekeres MA, Buckstein RJ, Zeidan AM. An agenda to advance research in myelodysplastic syndromes: a TOP 10 priority list from the first international workshop in MDS. Blood Advances 2023, 7: 2709-2714. PMID: 36260702, PMCID: PMC10333740, DOI: 10.1182/bloodadvances.2022008747.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCurrent landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS)
Bewersdorf J, Xie Z, Bejar R, Borate U, Boultwood J, Brunner A, Buckstein R, Carraway H, Churpek J, Daver N, Porta M, DeZern A, Fenaux P, Figueroa M, Gore S, Griffiths E, Halene S, Hasserjian R, Hourigan C, Kim T, Komrokji R, Kuchroo V, List A, Loghavi S, Majeti R, Odenike O, Patnaik M, Platzbecker U, Roboz G, Sallman D, Santini V, Sanz G, Sekeres M, Stahl M, Starczynowski D, Steensma D, Taylor J, Abdel-Wahab O, Xu M, Savona M, Wei A, Zeidan A. Current landscape of translational and clinical research in myelodysplastic syndromes/neoplasms (MDS): Proceedings from the 1st International Workshop on MDS (iwMDS) Of the International Consortium for MDS (icMDS). Blood Reviews 2023, 60: 101072. PMID: 36934059, DOI: 10.1016/j.blre.2023.101072.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsCell- and Tissue-Based TherapyEpigenomicsHumansMyelodysplastic SyndromesNeoplasmsProtein Processing, Post-TranslationalConceptsImmune checkpoint inhibitorsSpecific molecular alterationsNovel animal modelInnate immune systemCheckpoint inhibitorsImmune dysregulationMDS patientsClinical trialsNovel therapiesTherapeutic strategiesAnimal modelsGermline predispositionImmune systemMolecular alterationsClinical researchInternational ConsortiumNeoplasmsClinical workGenetic landscapeInternational WorkshopPatientsCurrent landscapePathogenesisTherapyDisease
2022
Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy. Leukemia 2022, 37: 240-243. PMID: 36437356, DOI: 10.1038/s41375-022-01766-z.Peer-Reviewed Original ResearchMeSH KeywordsAntimetabolites, AntineoplasticAzacitidineHumansLeukemia, Myeloid, AcuteMyelodysplastic SyndromesPrognosisTumor Suppressor Protein p53Finding consistency in classifications of myeloid neoplasms: a perspective on behalf of the International Workshop for Myelodysplastic Syndromes
Zeidan AM, Bewersdorf JP, Buckstein R, Sekeres MA, Steensma DP, Platzbecker U, Loghavi S, Boultwood J, Bejar R, Bennett JM, Borate U, Brunner AM, Carraway H, Churpek JE, Daver NG, Della Porta M, DeZern AE, Efficace F, Fenaux P, Figueroa ME, Greenberg P, Griffiths EA, Halene S, Hasserjian RP, Hourigan CS, Kim N, Kim TK, Komrokji RS, Kutchroo V, List AF, Little RF, Majeti R, Nazha A, Nimer SD, Odenike O, Padron E, Patnaik MM, Roboz GJ, Sallman DA, Sanz G, Stahl M, Starczynowski DT, Taylor J, Xie Z, Xu M, Savona MR, Wei AH, Abdel-Wahab O, Santini V. Finding consistency in classifications of myeloid neoplasms: a perspective on behalf of the International Workshop for Myelodysplastic Syndromes. Leukemia 2022, 36: 2939-2946. PMID: 36266326, DOI: 10.1038/s41375-022-01724-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsSelective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes
Fischer MA, Song Y, Arrate MP, Gbyli R, Villaume MT, Smith BN, Childress MA, Stricker TP, Halene S, Savona MR. Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes. Haematologica 2022, 108: 522-531. PMID: 35979721, PMCID: PMC9890032, DOI: 10.3324/haematol.2022.280631.Peer-Reviewed Original ResearchConceptsB-cell lymphoma 2Acute myeloid leukemiaMyeloid cell leukemia-1Myelodysplastic syndromeMDS subtypesHigh-risk myelodysplastic syndromeMCL1 inhibitionRisk myelodysplastic syndromesAnti-apoptotic protein B-cell lymphoma 2Protein B-cell lymphoma 2Effective clinical therapySelective inhibitorMDS patient samplesAttractive therapeutic opportunityBcl-xLExcess blastsOlder patientsClinical trialsMyeloid leukemiaMurine modelImpressive responseSignificant injuryAnti-apoptotic protein Bcl-xLLeukemia survivalLymphoma 2Targeting the EIF2AK1 signaling pathway rescues red blood cell production in SF3B1-mutant myelodysplastic syndromes with ringed sideroblasts
Adema V, Ma F, Kanagal-Shamanna R, Thongon N, Montalban-Bravo G, Yang H, Peslak SA, Wang F, Acha P, Sole F, Lockyer P, Cassari M, Maciejewski JP, Visconte V, Ganan-Gomez I, Song Y, Bueso-Ramos C, Pellegrini M, Tan TM, Bejar R, Carew JS, Halene S, Santini V, Al-Atrash G, Clise-Dwyer K, Garcia-Manero G, Blobel GA, Colla S. Targeting the EIF2AK1 signaling pathway rescues red blood cell production in SF3B1-mutant myelodysplastic syndromes with ringed sideroblasts. Blood Cancer Discovery 2022, 3: 554-567. PMID: 35926182, PMCID: PMC9894566, DOI: 10.1158/2643-3230.bcd-21-0220.Peer-Reviewed Original ResearchMeSH KeywordsAgedEIF-2 KinaseErythroid Precursor CellsHumansMyelodysplastic SyndromesPhosphoproteinsRNA Splicing FactorsSignal TransductionConceptsMyelodysplastic syndromeRed blood cell productionSF3B1-mutant myelodysplastic syndromesMDS-RSRinged sideroblastsBlood cell productionSF3B1 mutationsDevelopment of therapiesCell productionRed blood cellsRed blood cell maturationHematologic responseSignificant anemiaTransfusion dependencyIron overloadMDS subtypesElderly populationSide effectsBone marrowCell maturationIssue featurePatientsBlood cellsErythroid precursorsBlood cell maturation
2020
Editorial: Do not lose focus on myeloid biology in the era of COVID-19.
Halene S, Prebet T. Editorial: Do not lose focus on myeloid biology in the era of COVID-19. Current Opinion In Hematology 2020, 28: 71-72. PMID: 33394725, DOI: 10.1097/moh.0000000000000635.Commentaries, Editorials and LettersCyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro
He X, Dou A, Feng S, Roman-Rivera A, Hawkins C, Lawley L, Zhang J, Wunderlich M, Mizukawa B, Halene S, Patel A, Fang J. Cyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro. Experimental Hematology 2020, 86: 21-27.e2. PMID: 32437909, PMCID: PMC7335335, DOI: 10.1016/j.exphem.2020.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCyclosporineDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression Regulation, LeukemicHumansIkaros Transcription FactorLenalidomideLeukemia, Myeloid, AcuteMiceMice, Inbred NODMuscle ProteinsMyelodysplastic SyndromesNeoplasm ProteinsUp-RegulationXenograft Model Antitumor AssaysConceptsAcute myeloid leukemiaMDS/acute myeloid leukemiaMyelodysplastic syndromeT cell activationAML patient-derived xenograft modelsG protein-coupled receptor 68MDS/AML cellsPatient-derived xenograft modelsMDS/AML cell linesDegradation of IKZF1AML cell linesCell linesActivity of CaNBone marrow cellsMDS patientsPrimary bone marrow cellsHematologic malignanciesMyeloid leukemiaAML cellsLenalidomideXenograft modelDrug AdministrationSuppressive effectProsurvival pathwaysMarrow cellsHumanized mice as preclinical models for myeloid malignancies
Gbyli R, Song Y, Halene S. Humanized mice as preclinical models for myeloid malignancies. Biochemical Pharmacology 2020, 174: 113794. PMID: 31926939, DOI: 10.1016/j.bcp.2020.113794.Books
2018
SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells
Liang Y, Tebaldi T, Rejeski K, Joshi P, Stefani G, Taylor A, Song Y, Vasic R, Maziarz J, Balasubramanian K, Ardasheva A, Ding A, Quattrone A, Halene S. SRSF2 mutations drive oncogenesis by activating a global program of aberrant alternative splicing in hematopoietic cells. Leukemia 2018, 32: 2659-2671. PMID: 29858584, PMCID: PMC6274620, DOI: 10.1038/s41375-018-0152-7.Peer-Reviewed Original ResearchConceptsSplicing factorsRNA processingAlternative splicingGene productsSplicing factor SRSF2Gene regulatory eventsAberrant alternative splicingSplice alterationsRecurrent mutationsSplicing proteinsHITS-CLIPSR familyMRNA splicingSplicing genesHematopoietic differentiationRegulatory eventsImpairs hematopoietic differentiationMolecular explanationWidespread modificationSplicingHematopoietic cellsMutationsBinding eventsOncogenesisProtein
2015
SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition
Kim E, Ilagan JO, Liang Y, Daubner GM, Lee S, Ramakrishnan A, Li Y, Chung YR, Micol JB, Murphy ME, Cho H, Kim MK, Zebari AS, Aumann S, Park CY, Buonamici S, Smith PG, Deeg HJ, Lobry C, Aifantis I, Modis Y, Allain F, Halene S, Bradley RK, Abdel-Wahab O. SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition. Cancer Cell 2015, 27: 617-630. PMID: 25965569, PMCID: PMC4429920, DOI: 10.1016/j.ccell.2015.04.006.Peer-Reviewed Original ResearchThe regulatory role of serum response factor pathway in neutrophil inflammatory response
Taylor A, Halene S. The regulatory role of serum response factor pathway in neutrophil inflammatory response. Current Opinion In Hematology 2015, 22: 67-73. PMID: 25402621, PMCID: PMC4374983, DOI: 10.1097/moh.0000000000000099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementChromosomes, Human, Pair 5HematopoiesisHumansInflammationIntegrinsMyelodysplastic SyndromesNeutrophilsSerum Response FactorSignal TransductionConceptsSerum response factor pathwayRole of SRFLinear actin polymerizationEssential transcription factorCell-cell interactionsRas homolog family memberAberrant myeloid differentiationFactor pathwayT cell developmentActin cytoskeletonMultiple complex rolesRegulated processSRF pathwayTranscription factorsDiaphanous 1Actin polymerizationMyeloid cell functionChromosome 5Integrin activationIntegrin complexRegulatory roleMyeloid differentiationCommon genetic aberrationsLeukocyte adhesion deficiencyAdaptive immune system
2010
Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes
Wang R, Gross CP, Maggiore RJ, Halene S, Soulos PR, Raza A, Galili N, Ma X. Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes. Leukemia Research 2010, 35: 904-908. PMID: 21067809, PMCID: PMC3114277, DOI: 10.1016/j.leukres.2010.10.007.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromePatient characteristicsRefractory anemiaMultivariate logistic regression modelMultiple patient characteristicsPopulation-based studyUse of HMAsLogistic regression modelsElderly patientsExcess blastsMultilineage dysplasiaRefractory cytopeniaMDS patientsPatientsComorbiditiesAnemiaSyndromeHigher chanceRegression modelsHMAsAgentsIntroduction periodCytopeniasDysplasiaCancer
2009
Neighborhood socioeconomic status influences the survival of elderly patients with myelodysplastic syndromes in the United States
Wang R, Gross CP, Halene S, Ma X. Neighborhood socioeconomic status influences the survival of elderly patients with myelodysplastic syndromes in the United States. Cancer Causes & Control 2009, 20: 1369-1376. PMID: 19455395, PMCID: PMC2921772, DOI: 10.1007/s10552-009-9362-7.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overFemaleHumansMaleMyelodysplastic SyndromesResidence CharacteristicsSocial ClassSurvival AnalysisUnited StatesConceptsNeighborhood socioeconomic statusMyelodysplastic syndromeSocioeconomic statusElderly patientsHazard ratioMultivariate Cox proportional hazards modelCox proportional hazards modelSurvival of patientsPopulation-based studyRisk of deathRisk of mortalityProportional hazards modelImpact of SESLow socioeconomic statusCensus tractsPrognostic roleMDS patientsIndependent determinantsRefractory anemiaHistological subtypesHazards modelPatientsSES statusTractS scores