2023
When to use which molecular prognostic scoring system in the management of patients with MDS?
Kewan T, Bewersdorf J, Gurnari C, Xie Z, Stahl M, Zeidan A. When to use which molecular prognostic scoring system in the management of patients with MDS? Best Practice & Research Clinical Haematology 2023, 36: 101517. PMID: 38092484, DOI: 10.1016/j.beha.2023.101517.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInternational Prognostic Scoring SystemPrognostic scoring systemAcute myeloid leukemiaScoring systemRisk stratificationRecurrent molecular alterationsHigh-risk patientsAppropriate risk stratificationManagement of patientsRecurrent genetic mutationsIntensive therapyMyeloid leukemiaTreatment strategiesPrognostic toolDisease pathogenesisMolecular alterationsHematopoietic cancersClinical decisionHeterogeneous groupGenetic mutationsNext-generation sequencingPrognostic systemPatientsVariable propensitySubsequent revisionWhy do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS
Frumm S, Shimony S, Stone R, DeAngelo D, Bewersdorf J, Zeidan A, Stahl M. Why do we not have more drugs approved for MDS? A critical viewpoint on novel drug development in MDS. Blood Reviews 2023, 60: 101056. PMID: 36805300, DOI: 10.1016/j.blre.2023.101056.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeDNA methyltransferase inhibitorLow risk (LR) MDSHigh-risk myelodysplastic syndromeHigh transfusion needsRisk myelodysplastic syndromesCurrent treatment landscapeErythropoiesis-stimulating agentsNovel drug developmentHR-MDSTreatment landscapeTransfusion needsTargetable mutationsClinical trialsMDS pathogenesisNew agentsRing sideroblastsMore drugsUnmet needTherapy developmentDrug developmentMethyltransferase inhibitorFactor mutationsApprovalInflammation
2022
Hitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts
Bewersdorf J, Rampal R. Hitting the brakes on accelerated and blast-phase myeloproliferative neoplasms: current and emerging concepts. Hematology 2022, 2022: 218-224. PMID: 36485103, PMCID: PMC9820986, DOI: 10.1182/hematology.2022000341.Peer-Reviewed Original ResearchMeSH KeywordsBlast CrisisHumansLeukemia, Myeloid, AcuteMutationMyeloproliferative DisordersPrognosisConceptsMyeloproliferative neoplasmsBlast-phase MPNBlast-phase myeloproliferative neoplasmsAllogeneic hematopoietic cell transplantationBCR-ABL-negative myeloproliferative neoplasmsStages of clinical developmentMedian overall survivalHigh-risk molecular featuresHematopoietic cell transplantationCurative therapeutic modalityPrognosis of patientsAcute myeloid leukemiaMinority of patientsClinical trial enrollmentMPN-BPMyeloid blastsCurative intentHypomethylating agentsOverall survivalCell transplantationPeripheral bloodMyeloid leukemiaPalliative treatmentBone marrowClinical developmentSynthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-tkGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survivalTranslating recent advances in the pathogenesis of acute myeloid leukemia to the clinic
Bewersdorf J, Abdel-Wahab O. Translating recent advances in the pathogenesis of acute myeloid leukemia to the clinic. Genes & Development 2022, 36: 259-277. PMID: 35318270, PMCID: PMC8973851, DOI: 10.1101/gad.349368.122.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaAnti-Tim-3 antibodiesPathogenesis of acute myeloid leukemiaTargeting of acute myeloid leukemiaMolecular targeted approachesUnmet medical needAnti-CD47IDH1/2 inhibitorsHematologic malignanciesSplicing factor mutationsCellular therapyPreclinical meansImmune targetsTET2</i>FDA approvalTrispecific antibodyMenin inhibitionMedical needLeukemiaAntibodiesIDH1/2MalignancyTherapyPatientsGilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors
Numan Y, Rahman Z, Grenet J, Boisclair S, Bewersdorf JP, Collins C, Barth D, Fraga M, Bixby DL, Zeidan AM, Yilmaz M, Desai P, Mannis G, Deutsch YE, Abaza Y, Dinner S, Frankfurt O, Litzow M, Al‐Kali A, Foran JM, Sproat LZ, Jovanovic B, Daver N, Perl AE, Altman JK. Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors. American Journal Of Hematology 2022, 97: 322-328. PMID: 34981560, DOI: 10.1002/ajh.26447.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaRelapsed/Refractory Acute Myeloid LeukemiaComposite complete remission rateRefractory acute myeloid leukemiaLower median overall survivalComplete remission rateMedian overall survivalStem cell transplantCRC ratesLower CRCRefractory FLT3Median survivalRemission rateIntensive inductionOverall survivalCell transplantCombination therapyFLT3 inhibitorsFLT3 mutationsClinical activityUS CentersRetrospective analysisADMIRAL studyMitogen-activated protein kinase pathway
2021
A review of FLT3 inhibitors in acute myeloid leukemia
Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Reviews 2021, 52: 100905. PMID: 34774343, PMCID: PMC9846716, DOI: 10.1016/j.blre.2021.100905.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaFLT3 mutationsMyeloid leukemiaTreatment of AMLInhibitor maintenance therapyDrug resistance mechanismsCommon genetic aberrationsConsolidation chemotherapyRefractory FLT3Maintenance therapyPoor prognosisPrognostic implicationsStromal protectionFLT3 inhibitorsStandard inductionADMIRAL studyFLT3Genetic aberrationsLeukemiaResistance mechanismsMutationsMonotherapyChemotherapyPrognosisGilteritinib
2020
A complex karyotype and a genetic mutation in acute myeloid leukaemia
Bewersdorf JP, Siddon A, DiAdamo A, Zeidan AM. A complex karyotype and a genetic mutation in acute myeloid leukaemia. The Lancet 2020, 396: 2018. PMID: 33341145, DOI: 10.1016/s0140-6736(20)32543-5.Peer-Reviewed Original ResearchManagement of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole?
Bewersdorf JP, Zeidan AM. Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole? Expert Review Of Hematology 2020, 13: 1131-1142. PMID: 32876498, DOI: 10.1080/17474086.2020.1819233.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkersCombined Modality TherapyDisease ManagementDisease SusceptibilityDNA MethylationDrug DevelopmentDrug Resistance, NeoplasmHumansMolecular Targeted TherapyMutationMyelodysplastic SyndromesPrognosisRemission InductionRetreatmentTreatment FailureTreatment OutcomeConceptsHigh-risk myelodysplastic syndromeHMA failureMyelodysplastic syndromeHR-MDS patientsRisk myelodysplastic syndromesMainstay of treatmentImmune pathogenesisMost patientsComplete responseImmune therapyAbysmal prognosisNovel agentsTherapeutic approachesTherapeutic conceptsImmune evasionTreatment approachesPatientsGenetic testingSyndromePathogenesisTreatmentMolecular mechanismsRecent studiesFailureAnnual MeetingClinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience*
Bewersdorf JP, Shallis RM, Gowda L, Wei W, Hager K, Isufi I, Kim TK, Pillai MM, Seropian S, Podoltsev NA, Gore SD, Siddon AJ, Zeidan AM. Clinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience*. Leukemia & Lymphoma 2020, 61: 2180-2190. PMID: 32362171, PMCID: PMC7603787, DOI: 10.1080/10428194.2020.1759051.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMedian overall survivalTherapy-related malignanciesOverall survivalMyelodysplastic syndromeMyeloid leukemiaAllogeneic hematopoietic stem cell transplantLonger median overall survivalSingle-center retrospective studyComplex karyotypeHematopoietic stem cell transplantIntensive chemotherapy approachesYale Cancer CenterCharacteristics of patientsSingle-center experienceMinority of patientsStem cell transplantLong-term survivalLow response rateIntensive chemotherapyCenter experienceClinicopathologic characteristicsAdverse prognosisAML patientsCell transplantWide variation in use and interpretation of gene mutation profiling panels among health care providers of patients with myelodysplastic syndromes: results of a large web-based survey
Pine AB, Chokr N, Stahl M, Steensma DP, Sekeres MA, Litzow MR, Luger SM, Stone RM, Greenberg PL, Bejar R, Bewersdorf JP, Gore SD, Zeidan AM. Wide variation in use and interpretation of gene mutation profiling panels among health care providers of patients with myelodysplastic syndromes: results of a large web-based survey. Leukemia & Lymphoma 2020, 61: 1455-1464. PMID: 32026740, DOI: 10.1080/10428194.2020.1723013.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromeRisk stratificationMolecular profilingNext-generation sequencingWeb-based surveyRole of NGSManagement of patientsUtility of NGSEvidence-based guidelinesHealth care providersLarge web-based surveyMDS patientsPractice patternsTreatment decisionsCare providersResponse assessmentProviders' beliefsPatientsInstitutional guidelinesGene mutationsDiagnosisSyndromeTesting logisticsInterpretation of resultsWide variation
2019
Getting personal with myelodysplastic syndromes: is now the right time?
Chokr N, Pine AB, Bewersdorf JP, Shallis RM, Stahl M, Zeidan AM. Getting personal with myelodysplastic syndromes: is now the right time? Expert Review Of Hematology 2019, 12: 215-224. PMID: 30977414, PMCID: PMC6540985, DOI: 10.1080/17474086.2019.1592673.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMyelodysplastic syndromeNext-generation sequencingTherapy selectionPrognosis of MDSRole of NGSPrognosis of patientsRoutine clinical practiceMinimal residual diseaseRecurrent genetic abnormalitiesResidual diseaseBlood countDisease stagePeripheral bloodHematologic malignanciesPrognostic evaluationMDS pathogenesisRoutine managementTherapy decisionsHealthy individualsBone marrowClinical practiceCytological examinationPatientsScoring systemDiagnostic accuracy
2018
Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo
Fritscher J, Amberger D, Dyckhoff S, Bewersdorf J, Masouris I, Voelk S, Hammerschmidt S, Schmetzer H, Klein M, Pfister H, Koedel U. Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo. Frontiers In Immunology 2018, 9: 550. PMID: 29616039, PMCID: PMC5867309, DOI: 10.3389/fimmu.2018.00550.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell DegranulationCells, CulturedCentral Nervous SystemCromolyn SodiumHumansImmunity, InnateMaleMast CellsMeningitis, PneumococcalMiceMice, Inbred C57BLMice, TransgenicMutationPneumococcal InfectionsProto-Oncogene Proteins c-kitStreptococcus pneumoniaeStreptolysinsConceptsBone marrow-derived mast cellsCentral nervous systemSystemic infection in vivoMast cellsBone-marrow-derived mast cell degranulationMast cell engraftmentMouse bone marrow-derived mast cellsBacterial infectionsMarrow-derived mast cellsCerebrospinal fluidMutant mouse strainsMast cell-deficientExperimental pneumococcal meningitisMast cell stabilizerSystemic bacterial infectionInfection in vivoDisease phenotypeCell deficiencyCSF pleocytosisPneumococcal serotypesC-kitCell engraftmentPneumococcal meningitisMouse strainsNervous system