2024
Risk of bleeding in patients with essential thrombocythemia and extreme thrombocytosis
Venkat R, Redd R, Harris A, Aryee M, Marneth A, Kamaz B, Kim C, Wazir M, Weeks L, Stahl M, DeAngelo D, Lindsley R, Luskin M, Hobbs G, How J. Risk of bleeding in patients with essential thrombocythemia and extreme thrombocytosis. Blood Advances 2024, 8: 6043-6054. PMID: 39293089, PMCID: PMC11635702, DOI: 10.1182/bloodadvances.2024013777.Peer-Reviewed Original ResearchConceptsRisk of bleedingClinically relevant nonmajor bleedingEssential thrombocythemiaBleeding riskPlatelet countCumulative incidenceDana-Farber Cancer Institute and Massachusetts General HospitalAssociated with acquired von Willebrand syndromeCumulative incidence of thrombosisCumulative incidence of bleedingIncreased bleeding riskIncidence of bleedingReduced bleeding riskVon Willebrand syndromeIncidence of thrombosisNonmajor bleedingDNMT3A mutationsMassachusetts General HospitalThrombotic eventsDana-FarberDiabetes mellitusBleedingPatientsRisk factorsTreatment decisions
2023
Unlike TET2 and ASXL1, Co-Occurring DNMT3A Mutations Are Not Associated with Increased Age in JAK2-Mutant Myeloproliferative Neoplasms (MPNs)
How J, Marneth A, Kamaz B, Kim C, Neuberg D, Ren S, Wazir M, Weeks L, Stahl M, DeAngelo D, Lindsley R, Luskin M, Hormoz S, Mullally A. Unlike TET2 and ASXL1, Co-Occurring DNMT3A Mutations Are Not Associated with Increased Age in JAK2-Mutant Myeloproliferative Neoplasms (MPNs). Blood 2023, 142: 4521. DOI: 10.1182/blood-2023-179407.Peer-Reviewed Original ResearchJAK2-mutated myeloproliferative neoplasmsJAK2-mutated patientsFraction of patientsVariant allele fractionASXL1 mutationsDNMT3A mutationsMyeloproliferative neoplasmsConcomitant mutationsMyeloproliferative neoplasms diagnosisAssociated with increasing ageEssential thrombocythemiaPolycythemia veraDriver mutationsMyeloproliferative neoplasm driver mutationsNext generation sequencingCo-mutated patientsHomozygous JAK2 mutationPhenotypic driver mutationsClinical next generation sequencingJAK2-mutantMPL mutationsMF patientsClonal hematopoiesisPV patientsJAK2 mutationImpact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study
Santini V, Zeidan A, Fenaux P, Madanat Y, Berry T, Feller F, Sun L, Xia Q, Wan Y, Huang F, Savona M, Platzbecker U. Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study. Blood 2023, 142: 4603. DOI: 10.1182/blood-2023-179378.Peer-Reviewed Original ResearchLower-risk myelodysplastic syndromesPlacebo groupTransfusion independenceTI ratesHot spot mutationsPoor prognosisMyelodysplastic syndromeRed blood cell transfusion independenceASXL1 mutationsErythropoiesis-stimulating agentsPhase 3 studyStudy of patientsTI responsesPresence of mutationsSpecific mutationsClinical responseStudy entryClinical efficacyClinical benefitPeripheral bloodMutation subgroupsDNMT3A mutationsEpigenetic modifiersPatientsRUNX1 mutations
2015
Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation
Mayle A, Yang L, Rodriguez B, Zhou T, Chang E, Curry C, Challen G, Li W, Wheeler D, Rebel V, Goodell M. Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation. Blood 2015, 125: 629-638. PMID: 25416277, PMCID: PMC4304108, DOI: 10.1182/blood-2014-08-594648.Peer-Reviewed Original ResearchConceptsHematologic malignanciesDNMT3A mutationsB-cell acute lymphocytic leukemiaAcute lymphocytic leukemiaSpectrum of malignanciesAcute myeloid leukemiaStem cellsPreleukemic phenotypeMyelodysplastic syndromePoor prognosisMyeloid leukemiaLymphocytic leukemiaLymphoid malignanciesMouse modelIrradiated micePrimary myelofibrosisMalignancyPreleukemic cellsLoss of functionDNA methyltransferase 3AMalignant transformationHematopoietic stem cellsMyeloid diseasesLeukemiaLymphoid lineage
2013
DNMT3A mutation is a poor prognosis biomarker in AML: Results of a meta-analysis of 4500 AML patients
Shivarov V, Gueorguieva R, Stoimenov A, Tiu R. DNMT3A mutation is a poor prognosis biomarker in AML: Results of a meta-analysis of 4500 AML patients. Leukemia Research 2013, 37: 1445-1450. PMID: 23962568, DOI: 10.1016/j.leukres.2013.07.032.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAML patientsEuropean Leukemia NetDNMT3A mutationsIndependent adverse prognostic factorPoor prognosis biomarkerAdverse prognostic factorSubgroup of patientsPotential prognostic valueHigh-risk genotypesRecurrent molecular aberrationsDNMT3A mutational statusShorter OSShorter RFSYounger patientsPrognostic factorsRisk stratificationWorse prognosisPrognostic valueAML subtypesMyeloid leukemiaPrognosis biomarkerPatientsMolecular aberrationsRisk genotypes
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