2025
Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes
Rodriguez-Sevilla J, Ganan-Gomez I, Kumar B, Thongon N, Ma F, Chien K, Kim Y, Yang H, Loghavi S, Tan R, Adema V, Li Z, Tanaka T, Uryu H, Kanagal-Shamanna R, Al-Atrash G, Bejar R, Banerjee P, Lynn Cha S, Montalban-Bravo G, Dougherty M, Fernandez Laurita M, Wheeler N, Jia B, Papapetrou E, Izzo F, Dueñas D, McAllen S, Gu Y, Todisco G, Ficara F, Della Porta M, Jain A, Takahashi K, Clise-Dwyer K, Halene S, Bertilaccio M, Garcia-Manero G, Daher M, Colla S. Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes. Nature Communications 2025, 16: 3450. PMID: 40216768, PMCID: PMC11992119, DOI: 10.1038/s41467-025-58662-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsMyelodysplastic syndromeImmune escapeMyelodysplastic syndrome hematopoietic stem cellsNatural killer (NK) cellsAberrant hematopoietic stem cellsEarly-stage myelodysplastic syndromeDevelopment of myelodysplastic syndromeStage of myelodysplastic syndromeAdoptive cell therapyFunctional in vitro studiesNatural killer cellsTime of diagnosisPreclinical in vivo studiesPre-malignant clonesDisease-related comorbiditiesPre-malignant stageSlow down disease progressionRegenerate hematopoiesisClonal cytopeniaNK cellsImmune surveillanceKiller cellsHealthy donorsPharmacological therapy
2024
The dynamics of hematopoiesis over the human lifespan
Li H, Côté P, Kuoch M, Ezike J, Frenis K, Afanassiev A, Greenstreet L, Tanaka-Yano M, Tarantino G, Zhang S, Whangbo J, Butty V, Moiso E, Falchetti M, Lu K, Connelly G, Morris V, Wang D, Chen A, Bianchi G, Daley G, Garg S, Liu D, Chou S, Regev A, Lummertz da Rocha E, Schiebinger G, Rowe R. The dynamics of hematopoiesis over the human lifespan. Nature Methods 2024, 22: 422-434. PMID: 39639169, PMCID: PMC11908799, DOI: 10.1038/s41592-024-02495-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsHematopoietic stemProgenitor cellsClassification of acute myeloid leukemiaDifferentiation of hematopoietic stem cellsAssociated with poor prognosisAcute myeloid leukemiaHuman hematopoietic stemWave of hematopoiesisGene expression networksMyeloid leukemiaPoor prognosisLineage outputMultilineage capacityDynamics of hematopoiesisCell ontogenyStem cellsLineage primingFate decisionsModel organismsTranscriptomic statesExpression networksHuman lifespanTranscriptional programsHematopoiesisZinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease
Lessard S, Rimmelé P, Ling H, Moran K, Vieira B, Lin Y, Rajani G, Hong V, Reik A, Boismenu R, Hsu B, Chen M, Cockroft B, Uchida N, Tisdale J, Alavi A, Krishnamurti L, Abedi M, Galeon I, Reiner D, Wang L, Ramezi A, Rendo P, Walters M, Levasseur D, Peters R, Harris T, Hicks A. Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease. Scientific Reports 2024, 14: 24298. PMID: 39414860, PMCID: PMC11484757, DOI: 10.1038/s41598-024-74716-7.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsSickle cell diseaseTreatment of sickle cell diseaseFetal hemoglobinCell therapyReactivation of fetal hemoglobinCell diseaseMonths of follow-upStem cellsReactivate fetal hemoglobinResults of preclinical studiesPotential treatmentEngraftment in vivoAutologous cell therapyNovel cell therapiesVaso-occlusive crisisIncreased total hemoglobinErythroid progenyHealthy donorsPreclinical studiesClinical developmentFollow-upErythroid enhancerBCL11A erythroid enhancerGATAA motifsThe effect of plerixafor on autologous stem cell mobilization, cell viability, and apheresis challenges
Puzo C, Li P, Tormey C, Siddon A. The effect of plerixafor on autologous stem cell mobilization, cell viability, and apheresis challenges. Lab Medicine 2024, 56: 187-194. PMID: 39303673, DOI: 10.1093/labmed/lmae080.Peer-Reviewed Original ResearchAutologous stem cell transplantationHematopoietic stem cellsMultiple myelomaG-CSFMobilization failureDiffuse large B-cell lymphomaAutologous stem cell mobilizationLarge B-cell lymphomaGranulocyte colony-stimulating factorAutologous stem cell transplant patientsEfficacy of plerixaforStem cell mobilizationB-cell lymphomaStem cell transplantationEffects of plerixaforRetrospective chart reviewColony-stimulating factorYale-New Haven HospitalCell viabilityMultiple risk factorsHodgkin lymphomaNon-HodgkinMobilization regimenCell transplantationPlerixafor395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice
Braga C, Mancuso R, Thompson E, Oez H, Gudneppannavar R, Zhang P, Huang P, Egan M, Murray T, Krause D, Bruscia E. 395 Altered hematopoiesis and functional decline of hematopoietic stem cells in cystic fibrosis mice. Journal Of Cystic Fibrosis 2024, 23: s207-s208. DOI: 10.1016/s1569-1993(24)01235-9.Peer-Reviewed Original ResearchThe Benjamin Button effect on stem cells: Reversing the clock on aging immunity.
Conde L, Lucas C. The Benjamin Button effect on stem cells: Reversing the clock on aging immunity. Science Immunology 2024, 9: eadq0013. PMID: 38701191, DOI: 10.1126/sciimmunol.adq0013.Peer-Reviewed Original ResearchChronic lung inflammation disrupts the quiescent state of hematopoietic stem cells in a cystic fibrosis mouse model
Braga C, Mancuso R, Thompson E, Oez H, Gudneppanavar R, Zhang P, Huang P, Murray T, Egan M, Krause D, Bruscia E. Chronic lung inflammation disrupts the quiescent state of hematopoietic stem cells in a cystic fibrosis mouse model. The Journal Of Immunology 2024, 212: 0062_6002-0062_6002. DOI: 10.4049/jimmunol.212.supp.0062.6002.Peer-Reviewed Original ResearchHematopoietic stem cellsChronic lung inflammationLung inflammationCystic fibrosisBone marrowQuiescent state of HSCsProgression of CF lung diseaseResponse to airway infectionWT hematopoietic stem cellsExpansion of HSCsMultipotent progenitorsCystic fibrosis mouse modelStem cellsCF lung diseasePathways associated with proliferationNeutrophilic lung inflammationPro-inflammatory signatureFibrosis mouse modelATAC-sequencing analysisAirway infectionBM cellsMyeloid lineageLung diseaseMouse modelInflammationImpact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques
Lee B, Gin A, Wu C, Singh K, Grice M, Mortlock R, Abraham D, Fan X, Zhou Y, AlJanahi A, Choi U, DeRavin S, Shin T, Hong S, Dunbar C. Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques. Cell Stem Cell 2024, 31: 455-466.e4. PMID: 38508195, PMCID: PMC10997443, DOI: 10.1016/j.stem.2024.02.010.Peer-Reviewed Original ResearchLentiviral vectorsRhesus macaquesGFP-expressing lentiviral vectorsClonal dynamicsLong-term engrafting hematopoietic stem cellsLong-term engraftmentHematopoietic stem cellsAutologous transplantation modelClinically relevant differencesLT-HSCLT-HSCsCells long-termTransplantation modelLentiviral transductionP53 inhibitionAnimal modelsStem cellsGenetic modification approachesRelevant differencesClonalityHSCCellsMacaquesEngraftmentCD33Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model
Wang Y, Cho J, Kastrunes G, Buck A, Razimbaud C, Culhane A, Sun J, Braun D, Choueiri T, Wu C, Jones K, Nguyen Q, Zhu Z, Wei K, Zhu Q, Signoretti S, Freeman G, Hemberg M, Marasco W. Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model. IScience 2024, 27: 108879. PMID: 38327771, PMCID: PMC10847687, DOI: 10.1016/j.isci.2024.108879.Peer-Reviewed Original ResearchCAR-T cellsChimeric antigen receptorClear cell renal cell carcinomaHematopoietic stem cellsHuman leukocyte antigenTumor microenvironmentCarbonic anhydrase IXExhausted CD8<sup>+</sup> T cellsAnti-PD-L1 monoclonal antibodyCD34<sup>+</sup> hematopoietic stem cellsMouse modelCD8<sup>+</sup> T cellsEngineered CAR-T cellsTreatment of solid tumorsReversing ITMUnfavorable tumor microenvironmentImmunosuppressive tumor microenvironmentCell renal cell carcinomaOrthotopic mouse modelRenal cell carcinomaHuman clear cell renal cell carcinomaAntitumor immunityCAR-TCell carcinomaLeukocyte antigen
2023
LAIR-1 agonism as a therapy for acute myeloid leukemia
Lovewell R, Hong J, Kundu S, Fielder C, Hu Q, Kim K, Ramsey H, Gorska A, Fuller L, Tian L, Kothari P, Paucarmayta A, Mason E, Meza I, Manzanarez Y, Bosiacki J, Maloveste K, Mitchell N, Barbu E, Morawski A, Maloveste S, Cusumano Z, Patel S, Savona M, Langermann S, Myint H, Flies D, Kim T. LAIR-1 agonism as a therapy for acute myeloid leukemia. Journal Of Clinical Investigation 2023, 133: e169519. PMID: 37966113, PMCID: PMC10650974, DOI: 10.1172/jci169519.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaLeukemic stem cellsMyeloid leukemiaPatient-derived xenograft modelsHealthy hematopoietic stem cellsStem cellsCare therapyLAIR-1LSC survivalAML blastsAgonist antibodyTherapeutic strategiesXenograft modelLeukemic cellsTherapeutic potentialHematopoietic stem cellsEffective eradicationTherapyLeukemiaCell deathAgonismSignaling programsCellsPresence of collagenAntibodiesPhenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways
Papoin J, Yan H, Leduc M, Le Gall M, Narla A, Palis J, Steiner L, Gallagher P, Hillyer C, Gautier E, Mohandas N, Blanc L. Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways. American Journal Of Hematology 2023, 99: 99-112. PMID: 37929634, PMCID: PMC10877306, DOI: 10.1002/ajh.27145.Peer-Reviewed Original ResearchConceptsErythroid progenitor differentiationCell cycleErythroid progenitorsProgenitor differentiationMass spectrometry-based proteomicsFurther functional analysisSpectrometry-based proteomicsHuman erythroid progenitorsProtein machineryErythroid progenitor proliferationTerminal erythropoiesisProteomic characterizationHematopoietic stem cellsProteomic dataProgenitor populationsHuman erythropoiesisReticulocyte maturationFunctional analysisErythroid lineageOxidative phosphorylationProgenitor proliferationErythroid disordersMetabolic pathwaysAbsolute expressionStem cellsPhenotypic and Proteomic Characterization of the Human Erythroid Progenitor Continuum Reveal Dynamic Changes in Cell Cycle and in Metabolic Pathways
Papoin J, Yan H, Leduc M, le-Gall M, Narla A, Steiner L, Gallagher P, Hillyer C, Gauthier E, Narla M, Blanc L. Phenotypic and Proteomic Characterization of the Human Erythroid Progenitor Continuum Reveal Dynamic Changes in Cell Cycle and in Metabolic Pathways. Blood 2023, 142: 2455. DOI: 10.1182/blood-2023-189566.Peer-Reviewed Original ResearchCell cycleFaster cycling cellsProgenitor differentiationProgenitor populationsOxidative phosphorylationMass spectrometry-based proteomicsErythroid progenitorsS phaseProtein copy numbersSpectrometry-based proteomicsErythroid progenitor differentiationCycle-related genesG2/MTerminal erythropoiesisProgenitor biologyProteomic characterizationHematopoietic stem cellsE2F membersHuman erythropoiesisHuman bone marrowFunctional analysisErythroid lineageMurine erythropoiesisMetabolic pathwaysS transitionLuspatercept Modulates Inflammation in the Bone Marrow, Restores Effective Erythropoiesis/Hematopoiesis, and Provides Sustained Clinical Benefit Versus Epoetin Alfa (EA): Biomarker Analysis from the Phase 3 COMMANDS Study
Hayati S, Zeidan A, Garcia-Manero G, Platzbecker U, Ahsan A, Verma A, Aluri S, Guerrero M, Gandhi A, Suragani R, Vodala S. Luspatercept Modulates Inflammation in the Bone Marrow, Restores Effective Erythropoiesis/Hematopoiesis, and Provides Sustained Clinical Benefit Versus Epoetin Alfa (EA): Biomarker Analysis from the Phase 3 COMMANDS Study. Blood 2023, 142: 1845. DOI: 10.1182/blood-2023-178674.Peer-Reviewed Original ResearchBM mononuclear cellsLow-risk MDSEpoetin alfaWk 48Myelodysplastic syndromeWk 24Clinical benefitPg/Bone marrowErythroid precursorsITT populationIL-1Ring sideroblastsN-terminal pro-brain natriuretic peptideLower-risk myelodysplastic syndromesPro-brain natriuretic peptideHematopoietic stem cellsDysplastic erythroid precursorsRBC transfusion independencePhase 3 trialSuperior clinical benefitSerum cytokine analysisAnti-inflammatory signalingIL-10 signalingComplete blood countSecretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production
Kang Y, Paik H, Zhang S, Chen J, Olson O, Mitchell C, Collins A, Swann J, Warr M, Fan R, Passegué E. Secretory MPP3 reinforce myeloid differentiation trajectory and amplify myeloid cell production. Journal Of Experimental Medicine 2023, 220: e20230088. PMID: 37115584, PMCID: PMC10140385, DOI: 10.1084/jem.20230088.Peer-Reviewed Original ResearchConceptsGranulocyte/macrophage progenitorsHematopoietic stem cellsMyeloid differentiationMajor functional contributorsNovel regulatory functionLocal bone marrow (BM) microenvironmentSteady-state hematopoiesisDifferentiation trajectoriesRecent lineagesMyeloid cell productionCellular heterogeneityBone marrow microenvironmentRegulatory functionsFunctional contributorsMacrophage progenitorsSecretory cellsStem cellsMPP3Blood productionMarrow microenvironmentCell productionDifferentiationRapid productionDistinct subsetsMyelopoiesisCryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention
Krimmer S, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, Lee S, Lax I, Mi W, Schlessinger J. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300054120. PMID: 36943885, PMCID: PMC10068818, DOI: 10.1073/pnas.2300054120.Peer-Reviewed Original ResearchConceptsOncogenic KIT mutantsStem cell factorKIT mutantsHomotypic contactsCryo-EM analysisUnexpected structural plasticityLigand stem cell factorElectron microscopy structural analysisReceptor tyrosine kinase KITOncogenic mutantsHematopoietic stem cellsKIT dimerizationTyrosine kinase KITD5 regionPlasma membraneMutational analysisMutantsExtracellular domainGerm cellsHuman cancersSomatic gainCell factorStructural plasticityStem cellsKinase KIT
2022
Protocol to identify and analyze mouse and human quiescent hematopoietic stem cells using flow cytometry combined with confocal imaging
Qiu J, Menon V, Tzavaras N, Liang R, Ghaffari S. Protocol to identify and analyze mouse and human quiescent hematopoietic stem cells using flow cytometry combined with confocal imaging. STAR Protocols 2022, 3: 101828. PMID: 36595934, PMCID: PMC9676629, DOI: 10.1016/j.xpro.2022.101828.Peer-Reviewed Original ResearchAberrant EVI1 splicing contributes to EVI1-rearranged leukemia
Tanaka A, Nakano T, Nomura M, Yamazaki H, Bewersdorf J, Mulet-Lazaro R, Hogg S, Liu B, Penson A, Yokoyama A, Zang W, Havermans M, Koizumi M, Hayashi Y, Cho H, Kanai A, Lee S, Xiao M, Koike Y, Zhang Y, Fukumoto M, Aoyama Y, Konuma T, Kunimoto H, Inaba T, Nakajima H, Honda H, Kawamoto H, Delwel R, Abdel-Wahab O, Inoue D. Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. Blood 2022, 140: 875-888. PMID: 35709354, PMCID: PMC9412007, DOI: 10.1182/blood.2021015325.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaEVI1 isoformsSF3B1 mutationsAberrant 3' splice sitesSelf-renewal of hematopoietic stem cellsSplicing factor SF3B1Zinc finger domainExonic splicing enhancerIn-frame insertionCryptic branch pointPathogenesis of myeloid leukemiaPatient-derived cell linesHematopoietic stem cellsRNA-splicingSplicing enhancerSplice siteEpigenomic analysesMutant SF3B1Promoter usageExon 13Leukemic transformationSplice variantsGenomic alterationsUpregulated transcriptsToll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation
Ding P, Tan Q, Wei Z, Chen Q, Wang C, Qi L, Wen L, Zhang C, Yao C. Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation. Bone Research 2022, 10: 42. PMID: 35624094, PMCID: PMC9142495, DOI: 10.1038/s41413-022-00210-3.Peer-Reviewed Original ResearchToll-like receptorsSystemic chronic inflammationBone lossGut microbiotaSystemic inflammationChronic inflammationBone metabolismLow-grade systemic chronic inflammationActivation of TLRsInflammation-induced osteoclastogenesisOsteoclastic bone lossExpansion of CD4Low bone massSubsequent bone lossInflammatory cytokinesBone massT cellsInflammationOsteoclast differentiationBone marrowMyeloid-biased hematopoiesisImmune systemHematopoietic stem cellsSingle-cell RNA sequencingMice2017 – HUMAN HEMATOPOIETIC STEM CELL ONTOGENY ACROSS DEVELOPMENT AND MATURATION
Rowe G, Li H, Cote P, Kuoch M, Ezike J, Afanassiev A, Greenstreet L, Tarantino G, Zhang S, Whangbo J, Butty V, Moiso E, Falchetti M, Connelly G, Morris V, Wang D, Chen A, Bianchi G, Daley G, Garg S, Liu D, Chou S, Regev A, da Rocha E, Schiebinger G. 2017 – HUMAN HEMATOPOIETIC STEM CELL ONTOGENY ACROSS DEVELOPMENT AND MATURATION. Experimental Hematology 2022, 111: s39-s40. DOI: 10.1016/j.exphem.2022.07.049.Peer-Reviewed Original ResearchHematopoietic stem cellsAcute myeloid leukemiaHuman HSPCsAssociated with poor survivalHematopoietic stem cell stateHuman hematopoietic developmentUmbilical cord bloodAdult bone marrowMature effector cellsLineage-restricted progenitorsBlood diseasesTranscriptional programsCirculating blood cellsCord bloodEngraftment potentialFetal liverEffector cellsHematopoietic stemLymphoid lineagesMyeloid leukemiaHuman hematopoiesisHSPC populationsBone marrowHematopoietic systemPoor survival
2021
Autologous hematopoietic stem cell product contaminated with Salmonella due to occult salmonellosis in an asymptomatic donor
Jacobs JW, Guarente J, Hendrickson JE, Tormey CA, Bar N. Autologous hematopoietic stem cell product contaminated with Salmonella due to occult salmonellosis in an asymptomatic donor. Journal Of Clinical Apheresis 2021, 37: 316-319. PMID: 34953078, DOI: 10.1002/jca.21962.Peer-Reviewed Original ResearchConceptsCellular therapy productsHematopoietic stem cellsAllogeneic blood productsAutologous hematopoietic stem cellsHematopoietic stem cell productsPathogenic Gram-negative organismsNormal skin floraTherapy productsCase of SalmonellaStem cell productsGram-negative organismsAsymptomatic donorsTherapeutic dilemmaBlood productsPathogen reduction technologySkin floraHSC productsAdverse effectsCell productsPrior reportsSignificant reductionStem cellsSalmonellosisSalmonella bacteriaMost microorganisms
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