2024
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
Hong Y, Pasca S, Shi W, Puiu D, Lake N, Lek M, Ru M, Grove M, Prizment A, Joshu C, Platz E, Guallar E, Arking D, Gondek L. Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms. Nature Communications 2024, 15: 10133. PMID: 39578475, PMCID: PMC11584845, DOI: 10.1038/s41467-024-54443-3.Peer-Reviewed Original ResearchConceptsClonal hematopoiesis of indeterminate potentialClonal hematopoiesisVariant allele fractionHeteroplasmic variantsIndeterminate potentialMyeloid neoplasmsHeteroplasmyMultiple mutationsAllele fractionMutationsHigh-risk groupPathogenic risk factorsMarkersRisk score modelDeleteriousnessSpliceosomeHematologic malignanciesRisk stratificationNeoplasm developmentNeoplasmsNeoplasm incidenceRisk factorsVariantsMultiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy
Podszywalow-Bartnicka P, Neugebauer K. Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy. RNA Biology 2024, 21: 584-600. PMID: 38798162, PMCID: PMC11135835, DOI: 10.1080/15476286.2024.2346688.Peer-Reviewed Original ResearchConceptsARE-binding proteinsRNA-binding proteinsAU-rich elementsStress granulesBinding proteinTranslational regulation of mRNAsImpact alternative splicingCytoplasmic stress granulesProtein-RNA bindingAdaptation to microenvironmentProtein-RNA networksBinding to AU-rich elementsCancer cell proteomePost-transcriptional regulationAU-rich RNA-binding proteinsRegulation of mRNAsChemotherapy resistanceGene expression levelsSequence motifsProtein-RNAMRNA structureMature mRNATranslational regulationAlternative splicingCell proteomeRestrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support
Radford M, Estcourt L, Sirotich E, Pitre T, Britto J, Watson M, Brunskill S, Fergusson D, Dorée C, Arnold D. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Of Systematic Reviews 2024, 2024: cd011305. PMID: 38780066, PMCID: PMC11112982, DOI: 10.1002/14651858.cd011305.pub3.Peer-Reviewed Original ResearchConceptsRed blood cell transfusion strategyHaematopoietic stem cell transplantationLiberal transfusion strategyClinically significant bleedingRestrictive transfusion strategyNon-randomised studiesTransfusion strategyIntensive chemotherapyRandomised controlled trialsRed blood cellsSignificant bleedingAll-cause mortalityLength of hospital admissionAcute leukemiaHaematological malignanciesRisk of clinically significant bleedingHaematopoietic stem cell supportProspective non-randomised studyRisk ratioControlled trialsQuality of lifeStem cell supportStem cell transplantationMalignant haematological disordersCochrane Central Register of Controlled TrialsLow skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta‐analysis
Anabtawi N, Pasala M, Grimshaw A, Kharel P, Bal S, Godby K, Siwakoti A, Buford T, Bhatia S, Costa L, Williams G, Giri S. Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta‐analysis. Journal Of Cachexia Sarcopenia And Muscle 2024, 15: 1084-1093. PMID: 38558541, PMCID: PMC11154774, DOI: 10.1002/jcsm.13446.Peer-Reviewed Original ResearchConceptsLow skeletal muscle massNon-relapse mortalityProgression free survivalTreatment-related toxicityHaematological malignanciesOverall survivalSkeletal muscle massMuscle massEffects of low skeletal muscle massImpact of low skeletal muscle massIncreased risk of treatment-related toxicityPresence of low skeletal muscle massRisk of treatment-related toxicityHazard ratioAssociated with worse survival outcomesAssociated with worse OSDerSimonian-Laird random-effects modelModerate heterogeneityInferior overall survivalWorse survival outcomesConfidence intervalsRandom-effects modelFree survivalSolid malignanciesPre-published protocolLiquid biopsy‐based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results
Mata D, Lee J, Shanmugam V, Marcus C, Schrock A, Williams E, Ritterhouse L, Hickman R, Janovitz T, Patel N, Kroger B, Ross J, Mirza K, Oxnard G, Vergilio J, Elvin J, Benhamida J, Decker B, Xu M. Liquid biopsy‐based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results. Histopathology 2024, 84: 1224-1237. PMID: 38422618, DOI: 10.1111/his.15168.Peer-Reviewed Original ResearchConceptsNon-Hodgkin's lymphomaPlasma-cell neoplasmsAcute myeloid leukemiaCirculating tumor DNAHodgkin lymphomaMyelodysplastic syndromeHaematopoietic neoplasmsNext-generation sequencingTissue-based NGSMaximum somatic allele frequencyFoundationOne Liquid CDxTherapy-resistant clonesRelevant genomic alterationsPositive percent agreementPotential clinical utilityLymphoid malignanciesTumor DNAMyeloid leukemiaPlasma-cellsTissue biopsiesGenomic alterationsPathogenic alterationsLiquid biopsyMolecular profilingTP53A phase 2 trial of CD24Fc for prevention of graft-versus-host disease
Magenau J, Jaglowski S, Uberti J, Farag S, Riwes M, Pawarode A, Anand S, Ghosh M, Maciejewski J, Braun T, Devenport M, Lu S, Banerjee B, DaSilva C, Devine S, Zhang M, Burns L, Liu Y, Zheng P, Reddy P. A phase 2 trial of CD24Fc for prevention of graft-versus-host disease. Blood 2024, 143: 21-31. PMID: 37647633, PMCID: PMC10934299, DOI: 10.1182/blood.2023020250.Peer-Reviewed Original ResearchConceptsAcute graft-versus-host diseaseGraft-versus-host diseaseHematopoietic stem cell transplantationDose-limiting toxicityMUD hematopoietic stem cell transplantationGVHD-free survivalMultidose regimenMyeloablative conditioningHematologic malignanciesHuman leukocyte antigen-matched unrelated donorsPrevention of graft-versus-host diseaseAllogeneic hematopoietic stem cell transplantationCalcineurin inhibitor-based prophylaxisMatched controlsDose-escalation phaseSingle-dose regimensStem cell transplantationPhase 2 trialSustained drug exposureAssociated with higher ratesDamage-associated molecular patternsExpansion cohortDouble-blindPlacebo-controlledUnrelated donor
2023
Ten-Eleven-Translocation Genes in Cancer
Wang Y, Wang X, Lu J. Ten-Eleven-Translocation Genes in Cancer. Cancer Treatment And Research 2023, 190: 363-373. PMID: 38113007, DOI: 10.1007/978-3-031-45654-1_11.Peer-Reviewed Original ResearchMeSH Keywords5-MethylcytosineDNA MethylationDNA-Binding ProteinsHematologic NeoplasmsHumansMixed Function OxygenasesMutationProto-Oncogene ProteinsConceptsTET mutationsTen-ElevenBiochemical functionsTranslocation (TET) familyTranslocation geneHematopoietic malignanciesHematopoietic expansionGenesHuman cancersMutationsCritical roleImmune responseTET2Clonal hematopoiesisSolid cancersEpigenomeTET1TET3RNABiologyUnanswered questionsDNAHematopoiesisCooperateTETsStatin-induced mitochondrial priming sensitizes multiple myeloma cells to BCL2 and MCL1 inhibitors
Juarez D, Buono R, Matulis S, Gupta V, Duong M, Yudiono J, Paul M, Mallya S, Diep G, Hsin P, Lu A, Suh S, Dong V, Roberts A, Leverson J, Jalaluddin M, Liu Z, Bueno O, Boise L, Fruman D. Statin-induced mitochondrial priming sensitizes multiple myeloma cells to BCL2 and MCL1 inhibitors. Cancer Research Communications 2023, 3: 2497-2509. PMID: 37956312, PMCID: PMC10704957, DOI: 10.1158/2767-9764.crc-23-0350.Peer-Reviewed Original ResearchCurrent Clinical Practices and Challenges in Molecular Testing: A GOAL Consortium Hematopathology Working Group Report
Lee T, Aisner D, David M, Eno C, Gagan J, Gocke C, Guseva N, Haley L, Jajosky A, Jones D, Mansukhani M, Mroz P, Murray S, Newsom K, Paulson V, Roy S, Rushton C, Segal J, Senaratne T, Siddon A, Starostik P, Van Ziffle J, Wu D, Xian R, Yohe S, Kim A. Current Clinical Practices and Challenges in Molecular Testing: A GOAL Consortium Hematopathology Working Group Report. Blood Advances 2023, 7: 4599-4607. PMID: 37236162, PMCID: PMC10425685, DOI: 10.1182/bloodadvances.2023010149.Peer-Reviewed Original ResearchConceptsMolecular testingAcute casesHematologic malignanciesRapid turnaround timeTertiary care laboratoryAcute myeloid leukemiaCurrent clinical practiceMyeloid leukemiaTurnaround timeLymphoid processesClinical practicePatient careNGS panelCalendar daysClinical expectationsWorking Group ReportMost survey respondentsMalignancyCareReimbursementCase reimbursementSurvey respondentsGroup ReportTesting practicesDaysCardiothoracic complications of immune checkpoint inhibitors
Gosangi B, Wang Y, Rubinowitz A, Kwan J, Traube L, Gange C, Bader A. Cardiothoracic complications of immune checkpoint inhibitors. Clinical Imaging 2023, 102: 98-108. PMID: 37659356, DOI: 10.1016/j.clinimag.2023.08.001.Peer-Reviewed Educational MaterialsConceptsImmune checkpoint inhibitorsICI therapyCheckpoint inhibitorsOverall survivalTumor responseAdverse effectsDevelopment of irAEsNovel adverse effectsImproved overall survivalOverall patient outcomesICI administrationHematologic malignanciesPatient outcomesSolid tumorsIrAEsCancer treatmentGreater mortalityComplicationsTherapySurvivalInhibitorsMyocarditisPneumonitisPatientsMalignancyMolecular findings in myeloid neoplasms
Tran T, Siddon A. Molecular findings in myeloid neoplasms. International Journal Of Laboratory Hematology 2023, 45: 442-448. PMID: 37345257, DOI: 10.1111/ijlh.14118.Peer-Reviewed Original ResearchMeSH KeywordsHematologic NeoplasmsHumansLeukemia, Myeloid, AcuteMutationMyelodysplastic SyndromesMyeloproliferative DisordersConceptsAcute myeloid leukemiaMyeloid neoplasmsNext-generation sequencingMyeloproliferative neoplasmsInternational diagnostic guidelinesSomatic gene mutationsHematologic cancersMyeloid leukemiaDiagnostic guidelinesClinical relevanceMyeloid disordersPatient careNeoplasmsCytogenetic findingsMolecular findingsGene mutationsNew molecular technologiesMolecular technologiesMutationsLeukemiaCancerPrognosticationCliniciansFindingsModifier mutationsImpact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis
Ragon B, Shah M, D’Souza A, Estrada-Merly N, Gowda L, George G, de Lima M, Hashmi S, Kharfan-Dabaja M, Majhail N, Banerjee R, Saad A, Hildebrandt G, Mian H, Abid M, Battiwalla M, Lekakis L, Patel S, Murthy H, Nieto Y, Strouse C, Badawy S, Al Hadidi S, Dholaria B, Aljurf M, Vesole D, Lee C, Pawarode A, Gergis U, Miller K, Holmberg L, Afrough A, Solh M, Munshi P, Nishihori T, Anderson L, Wirk B, Kaur G, Qazilbash M, Shah N, Kumar S, Usmani S. Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis. Blood Advances 2023, 7: 2746-2757. PMID: 36827681, PMCID: PMC10275699, DOI: 10.1182/bloodadvances.2022009138.Peer-Reviewed Original ResearchMeSH KeywordsAdultHematologic NeoplasmsHumansLenalidomideMelphalanMultiple MyelomaNeoplasms, Second PrimaryTransplantation, AutologousUnited StatesConceptsSecond hematological malignanciesSecond primary malignanciesProgression-free survivalMultiple myelomaOverall survivalMaintenance therapyDevelopment of SPMsRisk of SPMAutologous hematopoietic stem cell transplantationInferior progression-free survivalHematopoietic stem cell transplantationHigh-dose melphalanMelphalan conditioning regimenSubsequent maintenance therapyStem cell transplantationFrequent primary causeCIBMTR analysisLenalidomide maintenanceAuto-HSCTConditioning regimenMedian survivalPrimary malignancyAdult patientsCell transplantationClinical trialsMicrofluidic 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 diversityThe COVID-19 Pandemic and In-Person Visit Rate Disruptions Among Patients With Hematologic Neoplasms in the US in 2020 to 2021
Goyal G, Lau K, Wang X, Davidoff A, Huntington S, Jamy O, Calip G, Shah H, Stephens D, Miksad R, Parikh R, Takvorian S, Neparidze N, Seymour E. The COVID-19 Pandemic and In-Person Visit Rate Disruptions Among Patients With Hematologic Neoplasms in the US in 2020 to 2021. JAMA Network Open 2023, 6: e2316642. PMID: 37273206, PMCID: PMC10242428, DOI: 10.1001/jamanetworkopen.2023.16642.Peer-Reviewed Original ResearchConceptsEarly pandemic monthsOral therapyOutpatient infusionsChronic lymphocytic leukemiaHematologic neoplasmsVisit ratesTelemedicine useCohort studyPandemic monthsLymphocytic leukemiaRetrospective observational cohort studyData cutoff datePerson medical careSubsequent cancer outcomesHalf of patientsObservational cohort studyMantle cell lymphomaCOVID-19COVID-19 pandemicNon-Hispanic whitesMedian ageActive treatmentCancer outcomesMultiple myelomaActive patientsPhase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies
Patel M, Donnellan W, Byrne M, Asch A, Zeidan A, Baer M, Fathi A, Kuykendall A, Zheng F, Walker C, Cheng L, Marando C, Savona M. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clinical Lymphoma Myeloma & Leukemia 2023, 23: 674-686. PMID: 37290996, DOI: 10.1016/j.clml.2023.05.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsHematologic NeoplasmsHumansLeukemia, Myeloid, AcutePrimary MyelofibrosisConceptsTreatment-emergent adverse eventsDose-limiting toxicityAdvanced hematologic malignanciesAcute myeloid leukemiaMyelodysplastic syndromeHematologic malignanciesCare agentsHigh-risk myelodysplastic syndromeMDS/myeloproliferative neoplasmPhase 1/2 studyEffective combination strategiesAdverse eventsComplete responseLymphoproliferative neoplasmsWeek 12Multiple myelomaSpleen volumeAcute leukemiaMyeloid leukemiaPreclinical modelsPatientsMyeloproliferative neoplasmsMoloney murine leukemia virus (PIM) kinasesMyelofibrosisKinase inhibitorsSpectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms
Xie Z, Chen E, Mendez L, Komrokji R, Zeidan A. Spectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms. The Cancer Journal 2023, 29: 130-137. PMID: 37195768, DOI: 10.1097/ppo.0000000000000656.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsClonal HematopoiesisHematologic NeoplasmsHematopoiesisHumansMutationMyelodysplastic SyndromesConceptsClonal hematopoiesisHigh-risk patientsRisk of progressionSuch patientsUndetermined significanceAge-related diseasesHematologic malignanciesClonal cytopeniaMyeloid neoplasmsHigh riskUnmet needMyeloid malignanciesNatural historyCH managementPatientsMalignancySignificant knowledge gapsRiskHematopoiesisCytopeniasNeoplasmsSyndromeIRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression
Tang H, Panse G, Braddock D, Perincheri S, Xu M, McNiff J. IRF8 may be a useful marker for blastic plasmacytoid dendritic cell neoplasm, especially with weak CD123 expression. Journal Of Cutaneous Pathology 2023, 50: 595-600. PMID: 37082914, DOI: 10.1111/cup.14439.Peer-Reviewed Original ResearchMeSH KeywordsDendritic CellsHematologic NeoplasmsHumansInterferon Regulatory FactorsInterleukin-3 Receptor alpha SubunitMaleMiddle AgedSkin NeoplasmsConceptsBlastic plasmacytoid dendritic cell neoplasmPlasmacytoid dendritic cell neoplasmDendritic cell neoplasmPunch biopsy specimenBiopsy specimenCell neoplasmsCase of BPDCNUseful markerTumor cellsTCL-1 expressionAtypical mononuclear cellsBone marrow involvementDiffuse dermal infiltrateDendritic cell lineagePotential diagnostic pitfallRegulatory factor 8TCL-1BPDCN casesCD123 expressionMarrow involvementDermal infiltrateCutaneous nodulesMyelodysplastic syndromeSkin nodulesMononuclear cellsA Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies
Chee C, Ooi M, Lee S, Sundar R, Heong V, Yong W, Ng C, Wong A, Lim J, Tan D, Soo R, Tan J, Yang S, Thura M, Al-Aidaroos A, Chng W, Zeng Q, Goh B. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Targeted Oncology 2023, 18: 391-402. PMID: 37060431, PMCID: PMC10192144, DOI: 10.1007/s11523-023-00962-w.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic AgentsHematologic NeoplasmsHumansLeukemia, Myeloid, AcuteMaximum Tolerated DoseNeoplasmsConceptsAcute myeloid leukemiaAdvanced solid tumorsFirst-in-human studyEuropean Leukemia NetworkSolid tumorsHematologic malignanciesTreatment-emergent adverse eventsHuman antibodiesDose-escalation cohortsDose-limiting toxicityGrade 2 vomitingPRL-3Refractory solid tumorsResponse Evaluation CriteriaSolid tumor patientsDose-expansion cohortReduced tumor growthFirst-in-humanPhase IStable diseaseStoma outputEvaluation CriteriaMyeloid leukemiaPharmacodynamic relationshipsAdverse eventsHow I treat AML incorporating the updated classifications and guidelines
Chaer F, Hourigan C, Zeidan A. How I treat AML incorporating the updated classifications and guidelines. Blood 2023, 141: 2813-2823. PMID: 36758209, PMCID: PMC10447497, DOI: 10.1182/blood.2022017808.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaClinical treatment guidelinesDaily clinical practiceInternational consensus classificationSomatic genetic abnormalitiesGerm-line predispositionWorld Health OrganizationTreatment guidelinesEuropean LeukemiaNetRisk stratificationHematologic malignanciesMyeloid leukemiaNovel therapiesMyeloid neoplasmsResponse assessmentClinical practiceNew treatmentsAML biologyConsensus classificationGenetic abnormalitiesTesting guidelinesHealth OrganizationGenetic driversRecent updatesTreatmentClinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.
Lee M, Peng S, Lee A, Wong S, Tay R, Li J, Tariq A, Goh C, Tan Y, Tan B, Teo C, Chan E, Ooi M, Chng W, Chee C, Ho C, Walsh R, Wong M, Su Y, Alexander L, Sethi S, Tan S, Chan Y, Tan K, Lee S, Chai L, Sundar R. Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients. Annals, Academy Of Medicine, Singapore 2023, 52: 8-16. PMID: 36730801, DOI: 10.47102/annals-acadmedsg.2022302.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralCOVID-19Hematologic NeoplasmsHumansImmunogenicity, VaccineNeoplasmsRNA, MessengerSARS-CoV-2Treatment OutcomeVaccinationConceptsSARS-CoV-2 mRNA vaccinesDoses of SARS-CoV-2 mRNA vaccinesMRNA vaccinesCancer patientsThird doseHaematological malignanciesLong-term immunogenicityCompared to patientsRisk of severe diseaseAnti-neoplastic treatmentActive cancer therapyVirus neutralisation assaySARS-CoV-2 infectionSystemic chemotherapyNo patientEarly administrationSeroconversion ratesVaccine immunogenicitySolid tumorsClinical efficacyClinical outcomesSevere infectionsCancer therapyHumoral responseActive treatment
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