2023
Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling
Feng X, Sun R, Lee M, Chen X, Guo S, Geng H, Müschen M, Choi J, Pereira J. Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling. ELife 2023, 12: e83533. PMID: 36912771, PMCID: PMC10042536, DOI: 10.7554/elife.83533.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsLymphotoxin beta receptorLeukemic cellsBeta receptorsLeukemic cell growthBone marrow microenvironmentStem cellsTransplant recipientsAML cellsMyeloblastic leukemiaMouse modelBone marrowLeukemia growthLymphotoxin α1β2Marrow microenvironmentPharmacological disruptionLymphopoiesisReceptorsHematopoietic outputMolecular mechanismsErythropoiesisDNA damage response pathwayCell growthCellsPhysiological mechanisms
2020
Cyclosporine 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 cellsVaccine and Cell-based Therapeutic Approaches in Acute Myeloid Leukemia
Agrawal V, Gbolahan OB, Stahl M, Zeidan AM, Zaid MA, Farag SS, Konig H. Vaccine and Cell-based Therapeutic Approaches in Acute Myeloid Leukemia. Current Cancer Drug Targets 2020, 20: 473-489. PMID: 32357813, DOI: 10.2174/1568009620666200502011059.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntibodies, MonoclonalAntigens, NeoplasmAntineoplastic Agents, ImmunologicalCancer VaccinesHematopoietic Stem Cell TransplantationHumansImmunotherapy, AdoptiveKiller Cells, NaturalLeukemia, Myeloid, AcuteReceptors, Chimeric AntigenT-Lymphocytes, CytotoxicTransplantation, HomologousTumor EscapeConceptsAcute myeloid leukemiaTumor-associated antigensImmune systemAML cellsMyeloid leukemiaTreatment of AMLAllogeneic stem cell transplantationEffective immunotherapeutic strategiesNatural killer cellsStem cell transplantationHumoral immune reactionsCell-based therapeutic approachesSurface receptor expressionAcute leukemia cellsDirect immunosuppressionImmunotherapeutic strategiesTreatment landscapeImmunotherapeutic approachesCellular immunotherapyKiller cellsCell transplantationClinical managementHematologic malignanciesReceptor expressionDecreased immunogenicity
2019
Identification of ZNF217 As an Essential Oncogenic Gene in B-Cell Acute Lymphoblastic Leukemia By CRISPR/Cas9-Based Library Screening
Qin X, Su R, Yang L, Chan A, Deng X, Qing Y, Klemm L, Müschen M, Chen C, Chen J. Identification of ZNF217 As an Essential Oncogenic Gene in B-Cell Acute Lymphoblastic Leukemia By CRISPR/Cas9-Based Library Screening. Blood 2019, 134: 1465. DOI: 10.1182/blood-2019-129849.Peer-Reviewed Original ResearchB-cell acute lymphoblastic leukemiaBCR-ABL1 fusionAcute lymphoblastic leukemiaAcute myeloid leukemiaAML cellsM6A regulatorsMLL-AF4 fusionAdult patientsLymphoblastic leukemiaPediatric B-cell acute lymphoblastic leukemiaEssential oncogenic roleM6A modificationMessenger RNACytogenetic characteristicsDismal survivalMyeloid leukemiaB cell progenitorsTherapeutic targetOncogenic roleSolid tumorsPatientsZinc finger protein 217B-lineageLeukemiaCytogenetic changesEffective Novel Fto Inhibitors Show Potent Anti-Cancer Efficacy and Suppress Drug Resistance
Su R, Dong L, Li Y, Han L, Gao M, Wunderlich M, Deng X, Li H, Gao L, Li C, Robison S, Tan B, Qing Y, Qin X, Prince E, Xie J, Qin H, Huang Y, Li W, Shen C, Sun J, Prakash K, Weng H, Huang H, Chen Z, Zhang B, Wu X, Olsen M, Müschen M, Marcucci G, Ravi S, Li L, Yang C, Li Z, Mulloy J, Wei M, Horne D, Chen J. Effective Novel Fto Inhibitors Show Potent Anti-Cancer Efficacy and Suppress Drug Resistance. Blood 2019, 134: 233. DOI: 10.1182/blood-2019-124535.Peer-Reviewed Original ResearchAML cell linesAnti-leukemic effectsAML cellsMouse modelDrug resistanceAcute myeloid leukemia patientsPotent anti-leukemic effectCell linesPotent anti-cancer efficacyAML cell viabilitySuppress drug resistanceAML mouse modelAnti-leukemia effectMyeloid leukemia patientsAnti-leukemic efficacyTransplantation mouse modelMurine AML cellsOnset of leukemiaFTO inhibitorsPotent therapeutic efficacyTyrosine kinase inhibitorsXenograft mouse modelAnti-leukemic activityFTO proteinAnti-AML efficacySF3B1 Mutations Induce Oncogenic IRAK4 Isoforms and Activate Targetable Innate Immune Pathways in MDS and AML
Choudhary G, Smith M, Pellagatti A, Bhagat T, Gordon S, Pandey S, Shah N, Aluri S, Booher R, Ramachandra M, Samson M, Pradhan K, Bowman T, Pillai M, Guha C, Wickrema A, Will B, Shastri A, Steidl U, Boultwood J, Starczynowski D, Verma A. SF3B1 Mutations Induce Oncogenic IRAK4 Isoforms and Activate Targetable Innate Immune Pathways in MDS and AML. Blood 2019, 134: 4224. DOI: 10.1182/blood-2019-124458.Peer-Reviewed Original ResearchToll-like receptorsAML cellsSF3B1 mutationsMDS/AML cellsInterleukin-1 receptor-associated kinaseMDS/AMLNF-kB activityInnate immune pathwaysInnate immune signalingNormal cellsDownstream oncogenic pathwaysLeukemic burdenCytokine releaseIRAK4 expressionNF-kBAML samplesImmune pathwaysSmall molecule inhibitorsNovartis PharmaceuticalsLeukemic cellsExon 6Mutation showTRAF6 activationAMLPharmacologic inhibition
2017
Dual Inhibition of Mdmx and Mdm2 Using an Alpha-Helical P53 Stapled Peptide (ALRN-6924) As a Novel Therapeutic Strategy in Acute Myeloid Leukemia
Carvajal L, Ben-Neriah D, Senecal A, Bernard L, Narayanagari S, Kenworthy C, Thiruthuvanathan V, Guerlavais V, Annis D, Bartholdy B, Will B, Anampa J, Mantzaris I, Aivado M, Singer R, Coleman R, Verma A, Steidl U. Dual Inhibition of Mdmx and Mdm2 Using an Alpha-Helical P53 Stapled Peptide (ALRN-6924) As a Novel Therapeutic Strategy in Acute Myeloid Leukemia. Blood 2017, 130: 795. DOI: 10.1182/blood.v130.suppl_1.795.795.Peer-Reviewed Original ResearchAML cell linesAML patient cellsAML cellsMDM2 inhibitionHealthy controlsLeukemic stemCell linesAge-matched healthy controlsWild-type p53Significant improved survivalProgenitor cellsAML xenograft modelStem cell-enriched populationAnti-leukemic effectsPatient cellsPatient undergoing treatmentAcute myeloid leukemiaCellular proliferationNovel therapeutic strategiesCell-enriched populationsTarget gene p21Primary cellsTP53 tumor suppressor geneObjective responseImproved survivalMUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs
Pyzer AR, Stroopinsky D, Rosenblatt J, Anastasiadou E, Rajabi H, Washington A, Tagde A, Chu JH, Coll M, Jiao AL, Tsai LT, Tenen DE, Cole L, Palmer K, Ephraim A, Leaf RK, Nahas M, Apel A, Bar-Natan M, Jain S, McMasters M, Mendez L, Arnason J, Raby BA, Slack F, Kufe D, Avigan D. MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs. Leukemia 2017, 31: 2780-2790. PMID: 28555079, PMCID: PMC5791150, DOI: 10.1038/leu.2017.163.Peer-Reviewed Original ResearchConceptsPD-L1 expressionAcute myeloid leukemiaAML cellsMiR-200cPD-L1/PDT cell-mediated lysisPD-L1 mRNA levelsLeukemia-specific T cellsPD-L1 levelsAnti-tumor immunityImmunosuppressive tumor microenvironmentMurine AML modelHuman AML cellsAML cell linesPotential therapeutic targetMicroRNA miR-200cMiR-34a levelsNanostring arraysMyeloid leukemiaT cellsTherapeutic targetMUC1 inhibitionTumor microenvironmentAML modelUpregulation of miRNAsMUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia.
Pyzer A, Stroopinsky D, Rajabi H, Washington A, Tagde A, Coll M, Fung J, Bryant M, Cole L, Palmer K, Somaiya P, Karp Leaf R, Nahas M, Apel A, Jain S, McMasters M, Mendez L, Levine J, Joyce R, Arnason J, Pandolfi P, Kufe D, Rosenblatt J, Avigan D. MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia. Blood 2017, 129: 1791-1801. PMID: 28126925, PMCID: PMC5813734, DOI: 10.1182/blood-2016-07-730614.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaSuppressor cellsAML cellsMyeloid leukemiaExtracellular vesiclesDonor peripheral blood mononuclear cellsAutologous T cell responsesCompetent antigen-presenting cellsMyeloid-derived suppressor cellsPeripheral blood mononuclear cellsReduced T-cell proliferationPresence of MDSCsExpansion of MDSCsT cell responsesBlood mononuclear cellsAntigen-presenting cellsPrimary AML cellsT cell proliferationExpansion of CD11bTumor-derived extracellular vesiclesMyeloid progenitor cellsMDSC populationsMDSC expansionImmune toleranceC57BL/6 mice
2016
Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells
Sumbayev V, Silva I, Blackburn J, Gibbs B, Yasinska I, Garrett M, Tonevitsky A, Ushkaryov Y. Expression of functional neuronal receptor latrophilin 1 in human acute myeloid leukaemia cells. Oncotarget 2016, 7: 45575-45583. PMID: 27322212, PMCID: PMC5216743, DOI: 10.18632/oncotarget.10039.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaTreatment of AMLPrimary human AML cellsHuman acute myeloid leukemia cellsAcute myeloid leukemia cellsLeukemia cellsHuman acute myeloid leukemiaHealthy leukocytesHuman AML cellsLatrophilin-1Myeloid leukemia cellsSerious medical burdenHuman monocytic leukemia cell lineMonocytic leukemia cell lineAML diagnosisSystemic diseaseMedical burdenMyeloid leukemiaAML cellsNovel biomarkersPotential new avenuesBone marrowLeukemia cell linesMalignant cellsBlood cancers
2013
Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells
Nieborowska-Skorska M, Slupianek A, Hoser G, Bolton-Gillespie E, Tulin A, Cerny-Reiterer S, Valent P, Muschen M, Sykes S, Skorski T. Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells. Blood 2013, 122: 810. DOI: 10.1182/blood.v122.21.810.810.Peer-Reviewed Original ResearchQuiescent leukemia stem cellsLeukemia progenitor cellsLeukemia stem cellsImatinib-naïveLeukemia cellsAML1-ETOBCR-ABL1PARP1 inhibitorsProgenitor cellsNormal cellsAnti-leukemia effectPositive AML cellsBCR-ABL1 T315I mutationInhibited colony formationAnti-proliferative effectsPARP inhibitor olaparibStem cellsModest inhibitory effectInhibition of PARPPeripheral bloodDisease burdenBone marrow nicheClinical trialsAML cellsT315I mutation
1989
c-myc amplification coexistent with activating N-ras point mutation in the biphenotypic leukemic cell line RED-3.
Mallet M, Mane S, Meltzer S, Needleman S. c-myc amplification coexistent with activating N-ras point mutation in the biphenotypic leukemic cell line RED-3. Leukemia 1989, 3: 511-5. PMID: 2659902.Peer-Reviewed Original ResearchConceptsCell linesMYC activationAcute myelogenous leukemiaN-ras point mutationsActivating point mutationC-MycN-rasAML patientsAcute leukemiaHL-60AML cellsMyelogenous leukemiaAggressive acute leukemiasLineage infidelityHuman tumorsDerivative cell linesPoint mutationsPatientsLeukemiaActivationSmall proportionCellsRed 3Protooncogene cMalignancy
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply