2024
Outcome of an Urban Cohort of North American Adult T-Cell Leukemia/Lymphoma Patients
Qureshi H, Kiwan A, Foss F, Kothari S, Huntington S, Isufi I, Seropian S, Sethi T. Outcome of an Urban Cohort of North American Adult T-Cell Leukemia/Lymphoma Patients. Blood 2024, 144: 6421-6421. DOI: 10.1182/blood-2024-211850.Peer-Reviewed Original ResearchAdult T-cell leukemia/lymphomaWhite blood cellsProgression free survivalWhite blood cell countOverall survivalHuman immunodeficiency virusComplete responseProgressive diseaseATLL patientsHD-MTXInstitutional cohortResponse to first line therapyAdult T-cell leukemia/lymphoma patientsMultivariate analysisMedian progression free survivalMedian time to relapseAllogeneic stem cell transplantationHuman T-cell lymphotropic virus type 1Median age of diagnosisMedian white blood cellMedian overall survivalHigh-dose methotrexateMulti-agent chemotherapyFirst line therapyMedian follow-upIdentification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies
Robinson M, Li Q, Zhang C, Zhan C, Cheng Z, Kume K, Cosgun K, Kothari S, Agadzhanian N, Nakada D, Müschen M. Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies. Blood 2024, 144: 4164-4164. DOI: 10.1182/blood-2024-205729.Peer-Reviewed Original ResearchB-ALL cell linesB-ALLB cellsCell linesTherapeutic vulnerabilitiesGene dependenciesNAD+ synthesisMature B-cell lymphomasElimination of B cellsTreatment of B-ALLNAD+ salvageChemotherapy-based regimensEffects of NAMPT inhibitionB-cell depletionB-cell lymphomaB-lymphoid malignanciesB-ALL cellsNAMPT inhibitorsInhibition of NAMPTATP-utilizing enzymesNAD+ salvage pathwayDrug repurposing platformNAD biosynthetic pathwayNear-complete ablationDe novo pathwayMechanism of Negative Feedback Regulation of Oncogenic BCR-Signaling in Mature B-Cell Lymphoma
Sun R, Lee J, Robinson M, Kume K, Zhan C, Cheng Z, Cosgun K, Chan L, Leveille E, Kothari S, Katz S, Ma N, Vykunta V, Shy B, Hodson D, Marson A, Vaidehi N, Müschen M. Mechanism of Negative Feedback Regulation of Oncogenic BCR-Signaling in Mature B-Cell Lymphoma. Blood 2024, 144: 3003-3003. DOI: 10.1182/blood-2024-211693.Peer-Reviewed Original ResearchB-cell lymphomaGC B cellsB-cell lymphoma cellsB cellsBCR signalingGerminal centersProteolytic cleavageNK cellsLymphoma cellsMantle cell lymphoma xenograftsAggressive B-cell lymphomasMature B-cell lymphomasB-cell lymphoma subtypesGerminal center B cellsSpontaneous germinal centersGlobal phosphoproteomic studiesActivation marker CD69Aggressiveness of diseaseCD25 surface expressionMechanism of negative feedback regulationB cell autoimmunityFollicular dendritic cellsHuman germinal centerCa2+ oscillationsExpressed increased levelsTargeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Berning P, Fonseca-Arce D, Leveille E, Kothari S, Davids M, Jellusova J, Müschen M. Targeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies. Blood 2024, 144: 1412. DOI: 10.1182/blood-2024-208598.Peer-Reviewed Original ResearchProtein degradationRepression of MYCTranscriptional repression of MYCTranscriptional repressionPromote survivalProteasome inhibitorsProtein degradation pathwaysCell typesN-terminal residuesInduce cell deathRefractory B-cell malignanciesB-cateninB-cell malignanciesRNAi screenInteractome studiesB cell selectionRepressive complexesGene dependenciesProteasomal degradationB cellsChemogenomic screensProteasome inhibitor bortezomibActivated mycDeletion of Ctnnb1Cell deathMetabolic Determinants of Ferroptosis in B-Cell Lymphoma
Leveille E, Bramson E, Robinson M, Bertomeu T, Chatr-Aryamontri A, Kothari S, Müschen M. Metabolic Determinants of Ferroptosis in B-Cell Lymphoma. Blood 2024, 144: 976-976. DOI: 10.1182/blood-2024-209077.Peer-Reviewed Original ResearchB-cell lymphomaB-cell malignanciesB cellsSensitivity to ferroptosisLipid membrane remodelingFerroptosis inducersMyeloid leukemiaSolid tumorsMembrane remodelingCRISPR screensGene dependenciesAssociated with significantly worse survivalTreatment of B-cell lymphomaB-cell lymphoma modelElimination of B cellsPUFA metabolismCysteine-glutamate antiporterCell deathMature splenic B cellsTherapy-resistant tumorsNon-apoptotic form of cell deathAnalysis of clinical dataDominant-negative p53Vulnerability to ferroptosisWhole-genome CRISPR screenEvaluation of prognostic factors in patients with high-risk classical Hodgkin lymphoma undergoing autologous transplantation
Epperla N, Huang Y, Cashen A, Vaughn J, Hanel W, Badar T, Barta S, Caimi P, Sethi T, Reddy N, Karmali R, Bello C, Chavez J, Kothari S, Hernandez-Ilizaliturri F, Svoboda J, Lansigan F, Glenn M, Cohen J, Sorge C, Christian B, Herrera A, Hamadani M, Costa L, Xavier A. Evaluation of prognostic factors in patients with high-risk classical Hodgkin lymphoma undergoing autologous transplantation. Blood Advances 2024, 8: 5458-5466. PMID: 39213424, PMCID: PMC11532746, DOI: 10.1182/bloodadvances.2024013743.Peer-Reviewed Original ResearchPrimary treatment failureAuto-HCTStable diseaseHodgkin lymphomaPartial responseCumulative incidence of non-relapse mortalityIncidence of non-relapse mortalityAssociated with inferior PFSEfficacy of auto-HCTAssociated with inferior OSAutologous hematopoietic cell transplantationEvaluation of prognostic factorsClassical Hodgkin lymphomaNon-relapse mortalityMulticenter retrospective cohortHigh-risk diseaseHematopoietic cell transplantationLong-term efficacyPatterns of failureUS medical centersProgression of diseaseInferior PFSMedian PFSInferior OSComplete responseHigh-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series
Epperla N, Zayac A, Landsburg D, Bock A, Nowakowski G, Ayers E, Girton M, Hu M, Beckman A, Li S, Medeiros L, Chang J, Kurt H, Sandoval-Sus J, Ansari-Lari M, Kothari S, Kress A, Xu M, Torka P, Sundaram S, Smith S, Naresh K, Karimi Y, Bond D, Evens A, Naik S, Kamdar M, Haverkos B, Karmali R, Farooq U, Vose J, Rubinstein P, Chaudhry A, Olszewski A. High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series. Blood Advances 2024, 8: 5355-5364. PMID: 39189932, PMCID: PMC11568788, DOI: 10.1182/bloodadvances.2024013791.Peer-Reviewed Original ResearchBaseline CNS involvementCentral nervous system recurrenceHigh-grade B-cell lymphomaCentral nervous systemB-cell lymphomaCNS involvementCNS recurrenceIncidence of CNS recurrenceRisk of CNS recurrenceCentral nervous system involvementMulti-institutional seriesNon-GCB subtypeBone marrow involvementMulticenter retrospective studyCNS-IPIRisk factor analysisMarrow involvementMYC rearrangementNon-GCBPrimary therapyCD5 expressionAutologous transplantationSurvival outcomesNo significant differenceNOS patientsReal World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma
Straining R, Foss F, Schiffer M, Amin K, Agarwal S, Isufi I, Huntington S, Kothari S, Seropian S, Girardi M, Sethi T. Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2024 PMID: 39368885, DOI: 10.1016/j.clml.2024.09.005.Peer-Reviewed Original ResearchT-cell lymphomaHeterogeneous group of lymphoid malignanciesGroup of lymphoid malignanciesPeripheral T-cell lymphomaAggressive T-cell lymphomaCutaneous T-cell lymphomaT cellsResponse rateR/R settingComplete responseLymphoid malignanciesPoor outcomeAnaplastic large cell lymphomaFrontline treatment regimensLarge cell lymphomaCombination of prednisoneHeterogeneous groupCell lymphomaChemotherapy optionsCaucasian patientsFirst-linePositive patientsTreatment regimensGrade 3LymphomaTuning Responses to Polatuzumab Vedotin in B-cell Lymphoma.
Leveille E, Kothari S, Cosgun K, Mlynarczyk C, Müschen M. Tuning Responses to Polatuzumab Vedotin in B-cell Lymphoma. Cancer Discovery 2024, 14: 1577-1580. PMID: 39228298, DOI: 10.1158/2159-8290.cd-24-0644.Peer-Reviewed Original ResearchCharacterizing the authorship of phase 3 randomized clinical trials in oncology, 1960-2023.
Warner J, Bakow B, Brown A, Choe J, Fan E, Ganta T, Glover M, Hadfield M, Hilton C, Khaki A, Kothari S, Lythgoe M, Nagpal S, Nguyen R, Noyd D, Riaz I, Rooney M, Sethi T, Singhi E, Rubinstein S. Characterizing the authorship of phase 3 randomized clinical trials in oncology, 1960-2023. Journal Of Clinical Oncology 2024, 42: 11079-11079. DOI: 10.1200/jco.2024.42.16_suppl.11079.Peer-Reviewed Original ResearchPhase 3 randomized clinical trialPhase 3 RCTsPrimary endpointClinical trialsEligible publicationsProlific authorsSystemic anticancer therapySuccess rateMann-Whitney U testStandard of carePositive publication biasTrial sample sizePositive resultsYear of publicationPublication biasTherapeutic advancesPrimary outcomeAuthorship patternAnticancer therapyExperimental armAuthor's outputMann-WhitneyU testInterquartile rangeAuthor informationEvaluation of the study of control arms in randomized clinical trials of cancer.
Jain S, Zauderer M, Sethi T, Schoen M, Rubinstein S, Nguyen R, Nagpal S, Mohan S, Madireddy S, Lythgoe M, Liang W, Kulkarni A, Kothari S, Hilal T, Hadfield M, Goyal G, Ganta T, Dholaria B, Brown A, Warner J. Evaluation of the study of control arms in randomized clinical trials of cancer. Journal Of Clinical Oncology 2024, 42: 11023-11023. DOI: 10.1200/jco.2024.42.16_suppl.11023.Peer-Reviewed Original ResearchRandomized clinical trialsSystemic anti-cancer therapyCancer randomized clinical trialsControl armSuccess rateClinical trials of cancerFisher's exact testAnti-cancer therapyTrial success ratesStudy publication yearExact testPatient convenienceRegimensClinical trialsHighest success rateExperimental armCancer typesCancerContext of treatmentPublication yearTrialsDoseNon-cancerEfficacyDyadsDependence of lymphopoiesis on efficient β-catenin degradation
Cosgun K, Jumaa H, Robinson M, Klemm L, Oulghazi S, Fonseca-Arce D, Xu L, Xiao G, Khanduja D, Chan L, Lee J, Kume K, Song J, Chan W, Chen J, Taketo M, Kothari S. Dependence of lymphopoiesis on efficient β-catenin degradation. The Journal Of Immunology 2024, 212: 1195_4936-1195_4936. DOI: 10.4049/jimmunol.212.supp.1195.4936.Peer-Reviewed Original ResearchIkaros zinc fingersLymphoid cellsB-cateninChIP-seq analysisSuppression of MYC expressionRegulate lineage specificationInduce cell deathConstitutively low levelsDeletion of ApcChIP-seqTcf factorsZinc fingerProteasomal degradationBinding motifNucleosome remodelingDestruction complexSpecific genesWnt/b-catenin pathwayLineage specificationCell deathMYC expressionSuperenhancersLymphoid developmentEpithelial lineageEpithelial cells
2023
Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma
Gerson J, Handorf E, Villa D, Gerrie A, Chapani P, Li S, Medeiros L, Wang M, Cohen J, Churnetski M, Hill B, Sawalha Y, Hernandez-Ilizaliturri F, Kothari S, Vose J, Bast M, Fenske T, Gari S, Maddocks K, Bond D, Bachanova V, Kolla B, Chavez J, Shah B, Lansigan F, Burns T, Donovan A, Wagner-Johnston N, Messmer M, Mehta A, Anderson J, Reddy N, Kovach A, Landsburg D, Glenn M, Inwards D, Ristow K, Karmali R, Kaplan J, Caimi P, Rajguru S, Evens A, Klein A, Umyarova E, Pulluri B, Amengual J, Lue J, Diefenbach C, Fisher R, Barta S. Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma. Blood Advances 2023, 7: 7393-7401. PMID: 37874912, PMCID: PMC10758713, DOI: 10.1182/bloodadvances.2023010757.Peer-Reviewed Original ResearchConceptsProgression-free survivalMantle cell lymphomaOverall survivalPleomorphic variantMedian progression-free survivalB-cell non-Hodgkin lymphomaOutcomes of patientsAutologous hematopoietic transplantationNon-Hodgkin lymphomaComplete responsePatient characteristicsPoor prognosisHematopoietic transplantationCell lymphomaSecondary objectiveMonthsPatientsLymphomaSurvivalHigher scoresPrimary objectivePrognosisTransplantationNeoplasmsRepurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies
Cosgun K, Robinson M, Oulghazi S, Xu L, Xiao G, Chan L, Lee J, Kume K, Leveille E, Arce D, Khanduja D, Feldhahn N, Song J, Chan W, Chen J, Taketo M, Schjerven H, Jellusova J, Kothari S, Davids M, Müschen M. Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies. Blood 2023, 142: 2818. DOI: 10.1182/blood-2023-190522.Peer-Reviewed Original ResearchFavorable safety profileSmall molecule inhibitorsT-lymphoid malignancyΒ-catenin degradationLymphoid malignanciesΒ-cateninInteractome studiesSafety profileClinical trialsMolecule inhibitorsLow nanomolar concentrationsΒ-catenin accumulationSolid tumorsRefractory B-cell malignanciesCell deathPK/PD profilesZinc finger proteinRefractory lymphoid malignanciesChIP-seq analysisPhase 2 trialMYC target genesT-cell lymphomaColony formationRapid nuclear accumulationWnt/β-catenin pathwayComputational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies
Li Q, Robinson M, Leveille E, Zhang C, Sun R, Cheng Z, Kume K, Cosgun K, Kothari S, Khanduja D, Nakada D, Müschen M. Computational Discovery and Validation of NAD+ Biosynthesis As Unique Vulnerability in B-Lymphoid Malignancies. Blood 2023, 142: 418. DOI: 10.1182/blood-2023-190269.Peer-Reviewed Original ResearchSmall molecule inhibitorsDrug discovery toolNAMPT inhibitorsCompound screenCell type-specific targetsCell linesMolecule inhibitorsPurine/pyrimidine metabolismTumor cell linesEnergy metabolismSalvage biosynthesis pathwaySolid tumor cell linesB cell developmentCellular energy metabolismB cell signalingAmino acid metabolismCell cycle arrestDiscovery toolDepletion of metabolitesBiosynthesis pathwayCompetitive fitnessRate-limiting enzymeNAMPT deletionConditional mouse modelEnergy stressGenetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells
Khanduja D, Robinson M, Arce D, Klemm L, Leveille E, Kothari S, Caeser R, Hodson D, Müschen M. Genetic Knockin Approaches to Reconstructing DLBCL-Subtypes from Human Germinal Center B-Cells. Blood 2023, 142: 1627. DOI: 10.1182/blood-2023-190634.Peer-Reviewed Original ResearchSecondary lymphoid organsGerminal center B cellsMYD88 L265P mutationLymphoid organsLymph nodesB cellsL265P mutationHuman germinal center B cellsDLBCL subtypesNSG miceTonsillar germinal center B cellsLymphoma developmentPreclinical testingLymphoid tissue inducer cellsTransgenic expressionPoor clinical outcomeWild-type mutationsGenetic mouse modelsExon 5GC B cellsNBSGW miceClinical outcomesLTi cellsLymphoid folliclesInducer cellsSeparation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies
Ketzer F, Klemm L, Robinson M, Loucks C, Arce D, Cosgun K, Kothari S, Müschen M. Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies. Blood 2023, 142: 1396. DOI: 10.1182/blood-2023-189221.Peer-Reviewed Original ResearchKinase ZAP70Transcriptional regulationTranscription factorsKinase SykDownstream activationT-cell signaling proteinsCRISPR/Cas9-mediated knockoutComparative proteomic analysisNegative selectionFunction of proteinsWild-type cellsCas9-mediated knockoutCo-expressed proteinsPre-malignant cellsT cell linesCellular fitnessTranscription machinerySLP-76Signaling proteinsMalignant transformationSignal transductionAberrant transcriptionProteomic analysisChIP-qPCRNovel key mechanismHigh-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study
Zayac A, Landsburg D, Hughes M, Bock A, Nowakowski G, Ayers E, Girton M, Hu M, Beckman A, Li S, Medeiros L, Chang J, Stepanovic A, Kurt H, Sandoval-Sus J, Ansari-Lari M, Kothari S, Kress A, Xu M, Torka P, Sundaram S, Smith S, Naresh K, Karimi Y, Epperla N, Bond D, Farooq U, Saad M, Evens A, Pandya K, Naik S, Kamdar M, Haverkos B, Karmali R, Oh T, Vose J, Nutsch H, Rubinstein P, Chaudhry A, Olszewski A. High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study. Blood Advances 2023, 7: 6381-6394. PMID: 37171397, PMCID: PMC10598493, DOI: 10.1182/bloodadvances.2023009731.Peer-Reviewed Original ResearchConceptsProgression-free survivalMulti-institutional retrospective studyHigh-grade B-cell lymphomaOverall survivalB-cell lymphomaComplete responseMYC rearrangementRetrospective studyBCL6 rearrangementsGerminal center B-cell immunophenotypeHigh serum lactate dehydrogenaseHigh-risk clinical factorsBetter progression-free survivalIntensive chemotherapy programsPoor performance statusStage IV diseaseFirst-line regimensMain prognostic factorsDose-intense chemotherapyHigh-grade morphologic featuresSerum lactate dehydrogenaseB-cell immunophenotypeDA-EPOCHR-CHOPMost patientsMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023)
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 10/2023). Small Methods 2023, 7 DOI: 10.1002/smtd.202370057.Peer-Reviewed Original ResearchMicrofluidic 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