2023
Diagnosis and Classification of Myelodysplastic Syndromes with Mutated TP53
Siddon A, Weinberg O. Diagnosis and Classification of Myelodysplastic Syndromes with Mutated TP53. Clinics In Laboratory Medicine 2023, 43: 607-614. PMID: 37865506, DOI: 10.1016/j.cll.2023.07.004.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeTP53 mutationsPrognosis of MDSCases of MDSPrognostic scoring systemNext-generation sequencingParticular next-generation sequencingAggressive diseasePoor outcomeTherapeutic managementTP53 disruptionMyeloid leukemiaMyeloid neoplasmsTherapeutic advancementsCytogenetic abnormalitiesMyeloid neoplasiaScoring systemDisease classificationMyeloid diseasesGene mutationsSyndromeDiseaseDiagnosisTP53Current 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 practicesDaysMolecular 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 ResearchConceptsAcute myeloid leukemiaMyeloid neoplasmsNext-generation sequencingMyeloproliferative neoplasmsInternational diagnostic guidelinesSomatic gene mutationsHematologic cancersMyeloid leukemiaDiagnostic guidelinesClinical relevanceMyeloid disordersPatient careNeoplasmsCytogenetic findingsMolecular findingsGene mutationsNew molecular technologiesMolecular technologiesMutationsLeukemiaCancerPrognosticationCliniciansFindingsModifier mutationsOptimizing Donor Chimerism Threshold for Next-Generation Sequencing Monitoring of Measurable Residual Disease Post-Allogeneic Stem Cell Transplantation for Myeloid Neoplasms
Puzo C, Tormey C, Rinder H, Siddon A. Optimizing Donor Chimerism Threshold for Next-Generation Sequencing Monitoring of Measurable Residual Disease Post-Allogeneic Stem Cell Transplantation for Myeloid Neoplasms. Transplantation And Cellular Therapy 2023, 29: 459.e1-459.e4. PMID: 37062510, DOI: 10.1016/j.jtct.2023.04.005.Peer-Reviewed Original ResearchConceptsAllogeneic stem cell transplantationStem cell transplantationDonor chimerismCell transplantationNGS testingPost allogeneic stem cell transplantationMeasurable residual diseaseNext-generation sequencingAcute myeloid leukemiaConditioning regimenRelated donorsMyelodysplastic syndromeResidual diseaseValidation cohortMyeloid leukemiaMyeloid neoplasmsNGS panelLogistic regressionPatientsChimerismSignificant predictorsCharacteristic curveTransplantationRegimenConservative thresholdMyeloid sarcoma with NPM1 mutation may be clinically and genetically distinct from AML with NPM1 mutation: a study from the Bone Marrow Pathology Group
de M, Wu L, Hirt C, Pihan G, Patel S, Tam W, Bueso-Ramos C, Kanagal-Shamanna R, Raess P, Siddon A, Narayanan D, Morgan E, Pinkus G, Mason E, Hsi E, Rogers H, Toth L, Foucar K, Hurwitz S, Bagg A, Rets A, George T, Orazi A, Arber D, Hasserjian R, Weinberg O, Group F. Myeloid sarcoma with NPM1 mutation may be clinically and genetically distinct from AML with NPM1 mutation: a study from the Bone Marrow Pathology Group. Leukemia & Lymphoma 2023, 64: 972-980. PMID: 36960680, DOI: 10.1080/10428194.2023.2185091.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid sarcomaOverall survivalNPM1 mutationsDe novo acute myeloid leukemiaBone Marrow Pathology GroupMulti-institutional cohort studyNovo acute myeloid leukemiaRetrospective multi-institutional cohort studyShorter overall survivalPoor overall survivalFrequent cytogenetic abnormalityCohort studyMyeloid leukemiaPathology groupCytogenetic abnormalitiesComplex karyotypeUnique genetic landscapeMutations of genesGene mutationsSarcomaGenetic landscapeHigher average numberMutationsLeukemia
2022
TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML
Weinberg OK, Siddon A, Madanat Y, Gagan J, Arber DA, Dal Cin P, Narayanan D, Ouseph MM, Kurzer JH, Hasserjian RP. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Advances 2022, 6: 2847-2853. PMID: 35073573, PMCID: PMC9092405, DOI: 10.1182/bloodadvances.2021006239.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeOverall survivalTP53 mutationsComplex karyotypeBlast countWorse outcomesTherapy-related MDS/acute myeloid leukemiaDiagnosis of AMLMDS/acute myeloid leukemiaTherapy-related myeloid neoplasmsTherapy-related casesTP53-mutated patientsDe novo diseaseMarrow blast countLower hemoglobin levelsWorse overall survivalCK patientsNovo diseaseDifferent disease categoriesClinicopathologic featuresHemoglobin levelsMDS patientsMultivariable analysisAggressive disease
2021
Laboratory evaluation and prognostication among adults and children with CEBPA‐mutant acute myeloid leukemia
Mendoza H, Podoltsev NA, Siddon AJ. Laboratory evaluation and prognostication among adults and children with CEBPA‐mutant acute myeloid leukemia. International Journal Of Laboratory Hematology 2021, 43: 86-95. PMID: 34288448, DOI: 10.1111/ijlh.13517.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCEBPA mutant acute myeloid leukemiaAcute myeloid leukemiaCEBPA mutationsMyeloid leukemiaLeukemogenic mutationsPositive prognostic impactSingle CEBPA mutationsSimilar survival outcomesNegative prognostic effectFLT3-ITD mutationLaboratory evaluationWild-type CEBPAMultiparameter flow cytometryGermline CEBPA mutationsFavorable prognosisPrognostic impactMutation presencePrognostic effectRisk stratificationSurvival outcomesGATA2 mutationsDistinct subtypesMolecular findingsCEBPA geneFlow cytometryClinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis
Shallis RM, Siddon AJ, Zeidan AM. Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis. Current Hematologic Malignancy Reports 2021, 16: 276-285. PMID: 33890194, DOI: 10.1007/s11899-021-00632-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPersistent monocytosisAppropriate diagnosisMyelomonocytic leukemiaPCM1-JAK2 fusionChronic myelomonocytic leukemiaAcute myeloid leukemiaAcute myelomonocytic leukemiaNegative predictive valuePurpose of ReviewInMyelodysplastic syndromeReactive monocytosisFGFR1 rearrangementAdult onsetMyeloid leukemiaMonocytosisBCR-ABL1Predictive valueASXL1 mutationsMyeloproliferative neoplasmsDiagnostic approachCytometric analysisMarrow tissuesLeukemiaDiagnosisMonocytic differentiation
2020
Monocytic Acute Myeloid Leukemias with KM2TA Translocations to Chromosome 17q that May Clinically Mimic Acute Promyelocytic Leukemia
Balbuena-Merle RI, Tormey CA, DiAdamo A, Rinder HM, Siddon AJ. Monocytic Acute Myeloid Leukemias with KM2TA Translocations to Chromosome 17q that May Clinically Mimic Acute Promyelocytic Leukemia. Lab Medicine 2020, 52: 290-296. PMID: 32984885, DOI: 10.1093/labmed/lmaa078.Peer-Reviewed Original ResearchConceptsAcute promyelocytic leukemiaAcute myeloid leukemiaMyeloid leukemiaPromyelocytic leukemiaMonocytic acute myeloid leukemiaTrans retinoic acidClinical presentationPrognostic implicationsPrognostic significanceLaboratory pictureCorrect diagnosisDistinct chemotherapyLeukemiaLeukemic entitiesRetinoic acidGene translocationMonocytic differentiationChromosome 17qTranslocationChemotherapyDiagnosisClinical 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 transplantIsolated trisomy 11 in patients with acute myeloid leukemia – is the prognosis not as grim as previously thought?*
Bewersdorf JP, Shallis RM, Diadamo A, Gowda L, Podoltsev NA, Siddon A, Zeidan AM. Isolated trisomy 11 in patients with acute myeloid leukemia – is the prognosis not as grim as previously thought?*. Leukemia & Lymphoma 2020, 61: 2254-2257. PMID: 32338096, PMCID: PMC7485109, DOI: 10.1080/10428194.2020.1755858.Peer-Reviewed Original Research
2015
Impact of Molecular Clonality on Survival in Acute Myeloid Leukemia
Schulz W, Durant T, Rinder H, Tormey C, Torres R, Smith B, Hager K, Howe J, Siddon A. Impact of Molecular Clonality on Survival in Acute Myeloid Leukemia. Blood 2015, 126: 1385. DOI: 10.1182/blood.v126.23.1385.1385.Peer-Reviewed Original ResearchDe novo acute myeloid leukemiaNovo acute myeloid leukemiaAcute myeloid leukemiaMolecular clonalityAML patientsTumor heterogeneityMyeloid leukemiaNext-generation sequencingNormal-risk subjectsAdverse prognostic indicatorTime of diagnosisFurther prospective studiesLong-term outcomesFLT3-ITD mutationHigh-risk groupChoice of therapyFirst prospective evidenceLimited clinical utilityHigh-risk classificationEarly survivalStudy patientsOverall survivalPatient agePatient subsetsInitial diagnosisPathology Consultation on Gene Mutations in Acute Myeloid Leukemia
Ziai JM, Siddon AJ. Pathology Consultation on Gene Mutations in Acute Myeloid Leukemia. American Journal Of Clinical Pathology 2015, 144: 539-554. PMID: 26386075, DOI: 10.1309/ajcp77zfpuqgygwy.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyeloid leukemiaGene mutationsTypes of AMLNormal acute myeloid leukemiaAggressive chemotherapy regimensMinimal residual diseaseChemotherapy regimensDisease courseImmunophenotypic featuresResidual diseaseTherapeutic regimensPatient prognosisPrognostic informationTherapeutic implicationsAML classificationIndividualized approachPathology consultationFatal diseasePrognosisHeterogeneous groupRelevant gene mutationsDiseaseLaboratory evaluationRegimens