Featured Publications
In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformation
2024
Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Integrated genetic, epigenetic, and immune landscape of TP53 mutant AML and higher risk MDS treated with azacitidine. Therapeutic Advances In Hematology 2024, 15: 20406207241257904. PMID: 38883163, PMCID: PMC11180421, DOI: 10.1177/20406207241257904.Peer-Reviewed Original ResearchHigher-risk myelodysplastic syndromesAcute myeloid leukemiaBone marrowMutation statusImmune landscapeImmunological landscapeAnti-PD-L1 antibody durvalumabHR-MDS patientsWild-type acute myeloid leukemiaTP53-mutant acute myeloid leukemiaMutant acute myeloid leukemiaAzacitidine-based therapyWild-type patientsImmune checkpoint proteinsImmune checkpoint expressionT cell populationsWild-typeStatistically significant decreaseAZA therapyImmunosuppressive microenvironmentPD-L1Mutant patientsDNA methylation arraysCheckpoint expressionMyelodysplastic syndrome
2023
A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents
Bewersdorf J, Shallis R, Sharon E, Park S, Ramaswamy R, Roe C, Irish J, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A multicenter phase Ib trial of the histone deacetylase inhibitor entinostat in combination with pembrolizumab in patients with myelodysplastic syndromes/neoplasms or acute myeloid leukemia refractory to hypomethylating agents. Annals Of Hematology 2023, 103: 105-116. PMID: 38036712, DOI: 10.1007/s00277-023-05552-4.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAcute myeloid leukemiaMarrow complete remissionPhase Ib trialAdverse eventsIb trialDose escalationNCI Cancer Therapy Evaluation ProgramAcute myeloid leukemia refractoryHematologic adverse eventsProtocol-defined responseDose level 1Anti-PD1 therapyAnti-PD1 antibodyDose-escalation designLimited clinical efficacySystems immunology approachHistone deacetylase inhibitor entinostatLeukemia refractoryMCR patientsComplete remissionRespiratory failureSuppressor cellsEscalation designClinical efficacy
2022
Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy
Zeidan A, Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Halene S, Haferlach T, Fox B. Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy. Leukemia 2022, 37: 240-243. PMID: 36437356, DOI: 10.1038/s41375-022-01766-z.Peer-Reviewed Original ResearchA Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure
Bewersdorf J, Shallis R, Sharon E, Caldwell A, Wei W, Yacoub A, Madanat Y, Zeidner J, Altman J, Odenike O, Yerrabothala S, Kovacsovics T, Podoltsev N, Halene S, Little R, Piekarz R, Gore S, Kim T, Zeidan A. A Multi-Center Phase Ib Trial of the Histone Deactylase Inhibitor (HDACi) Entinostat in Combination with Anti-PD1 Antibody Pembrolizumab in Patients with Refractory/Relapsed Myelodysplastic Syndromes (RR-MDS) or Oligoblastic Acute Myeloid Leukemia (RR-AML) after Hypomethylating Agent (HMA) Failure. Blood 2022, 140: 9084-9086. DOI: 10.1182/blood-2022-158626.Peer-Reviewed Original ResearchSelective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes
Fischer MA, Song Y, Arrate MP, Gbyli R, Villaume MT, Smith BN, Childress MA, Stricker TP, Halene S, Savona MR. Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes. Haematologica 2022, 108: 522-531. PMID: 35979721, PMCID: PMC9890032, DOI: 10.3324/haematol.2022.280631.Peer-Reviewed Original ResearchConceptsB-cell lymphoma 2Acute myeloid leukemiaMyeloid cell leukemia-1Myelodysplastic syndromeMDS subtypesHigh-risk myelodysplastic syndromeMCL1 inhibitionRisk myelodysplastic syndromesAnti-apoptotic protein B-cell lymphoma 2Protein B-cell lymphoma 2Effective clinical therapySelective inhibitorMDS patient samplesAttractive therapeutic opportunityBcl-xLExcess blastsOlder patientsClinical trialsMyeloid leukemiaMurine modelImpressive responseSignificant injuryAnti-apoptotic protein Bcl-xLLeukemia survivalLymphoma 2Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?
Shallis RM, Bewersdorf JP, Stahl MF, Halene S, Zeidan AM. Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia? Cancers 2022, 14: 2434. PMID: 35626039, PMCID: PMC9140008, DOI: 10.3390/cancers14102434.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCD47/SIRPαIntensive induction therapyAvailable therapeutic optionsStem cell transplantationStandard of careAvailable clinical dataTesting of agentsInduction therapyMedian overallRefractory settingAggressive treatmentTim-3Immune checkpointsPreclinical rationaleTherapeutic optionsCell transplantationEfficacy dataClinical dataPatientsMolecular subgroupsTherapeutic agents
2021
Comprehensive Clinicopathologic and Molecular Analysis of Mast Cell Leukemia With Associated Hematologic Neoplasm: A Report and In-Depth Study of 5 Cases
Li P, Biancon G, Patel T, Pan Z, Kothari S, Halene S, Prebet T, Xu ML. Comprehensive Clinicopathologic and Molecular Analysis of Mast Cell Leukemia With Associated Hematologic Neoplasm: A Report and In-Depth Study of 5 Cases. Frontiers In Oncology 2021, 11: 730503. PMID: 34589432, PMCID: PMC8474637, DOI: 10.3389/fonc.2021.730503.Peer-Reviewed Original ResearchMast cell leukemiaAssociated hematologic neoplasmCell leukemiaHematologic neoplasmsAcute myeloid leukemiaPaucity of casesWhole-exome sequencingAdditional patientsCase seriesAggressive entityRare tumorMyeloid leukemiaAvailable tumorsComprehensive clinicopathologicLeukemiaPatientsNeoplasmsTumorsMolecular analysisClinicopathologicSequencing resultsCases
2020
Cyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro
He X, Dou A, Feng S, Roman-Rivera A, Hawkins C, Lawley L, Zhang J, Wunderlich M, Mizukawa B, Halene S, Patel A, Fang J. Cyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro. Experimental Hematology 2020, 86: 21-27.e2. PMID: 32437909, PMCID: PMC7335335, DOI: 10.1016/j.exphem.2020.05.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCyclosporineDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression Regulation, LeukemicHumansIkaros Transcription FactorLenalidomideLeukemia, Myeloid, AcuteMiceMice, Inbred NODMuscle ProteinsMyelodysplastic SyndromesNeoplasm ProteinsUp-RegulationXenograft Model Antitumor AssaysConceptsAcute myeloid leukemiaMDS/acute myeloid leukemiaMyelodysplastic syndromeT cell activationAML patient-derived xenograft modelsG protein-coupled receptor 68MDS/AML cellsPatient-derived xenograft modelsMDS/AML cell linesDegradation of IKZF1AML cell linesCell linesActivity of CaNBone marrow cellsMDS patientsPrimary bone marrow cellsHematologic malignanciesMyeloid leukemiaAML cellsLenalidomideXenograft modelDrug AdministrationSuppressive effectProsurvival pathwaysMarrow cells
2019
The minimal that kills: Why defining and targeting measurable residual disease is the “Sine Qua Non” for further progress in management of acute myeloid leukemia
Bewersdorf JP, Shallis RM, Boddu PC, Wood B, Radich J, Halene S, Zeidan AM. The minimal that kills: Why defining and targeting measurable residual disease is the “Sine Qua Non” for further progress in management of acute myeloid leukemia. Blood Reviews 2019, 43: 100650. PMID: 31883804, DOI: 10.1016/j.blre.2019.100650.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaMyeloid leukemiaHard clinical outcomesClinical trial evidenceMeasurable residual diseaseResidual leukemic cellsRisk of relapseApprovable endpointsMRD statusDeep remissionMorphologic remissionMRD assessmentOverall survivalMRD levelsClinical outcomesDisease relapseInitial treatmentResidual diseaseTrial evidenceClinical trialsTreatment decisionsSurrogate endpointsBone marrowPreemptive interventionLeukemic cellsLAM-003, a new drug for treatment of tyrosine kinase inhibitor–resistant FLT3-ITD–positive AML
Beeharry N, Landrette S, Gayle S, Hernandez M, Grotzke JE, Young PR, Beckett P, Zhang X, Carter BZ, Andreeff M, Halene S, Xu T, Rothberg J, Lichenstein H. LAM-003, a new drug for treatment of tyrosine kinase inhibitor–resistant FLT3-ITD–positive AML. Blood Advances 2019, 3: 3661-3673. PMID: 31751472, PMCID: PMC6880894, DOI: 10.1182/bloodadvances.2019001068.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalDose-Response Relationship, DrugDrug Resistance, NeoplasmDrug SynergismEpigenesis, GeneticFms-Like Tyrosine Kinase 3Gene DuplicationGene Expression Regulation, LeukemicHumansLeukemia, Myeloid, AcuteMiceMutationProtein Kinase InhibitorsConceptsAcute myeloid leukemiaAML cell linesFLT3 inhibitorsFLT3-ITDSingle agentPositive acute myeloid leukemiaFLT3 inhibitor therapyStromal-conditioned mediumInitial clinical responseInternal tandem duplication mutationsFLT3-ITD patientsPoor patient prognosisXenograft mouse modelCell linesFLT3 kinase inhibitorsTandem duplication mutationsDiscovery of synergyWide CRISPR screenClinical responseTyrosine kinase receptorsInhibitor therapyPreclinical findingsBcl-2 inhibitorsMechanisms of resistancePatient prognosis
2017
Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life
Wang R, Zeidan AM, Halene S, Xu X, Davidoff AJ, Huntington SF, Podoltsev NA, Gross CP, Gore SD, Ma X. Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life. Journal Of Clinical Oncology 2017, 35: jco.2017.72.714. PMID: 28783450, PMCID: PMC5648174, DOI: 10.1200/jco.2017.72.7149.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaDays of lifeEnd of lifeLife careHospice careOlder patientsHospice enrollmentMyeloid leukemiaIntensive care unit admissionMultivariable logistic regression analysisOlder adultsLate hospice enrollmentCare unit admissionRetrospective cohort studyUse of chemotherapyIntensive care unitHealth care useLogistic regression analysisYears of ageUnit admissionAggressive treatmentCohort studyOverall cohortAML diagnosisCare unit
2011
Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia
Bajaj R, Xu F, Xiang B, Wilcox K, DiAdamo AJ, Kumar R, Pietraszkiewicz A, Halene S, Li P. Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia. Molecular Cytogenetics 2011, 4: 3. PMID: 21251322, PMCID: PMC3031273, DOI: 10.1186/1755-8166-4-3.Peer-Reviewed Original ResearchArray comparative genomic hybridizationCopy number alterationsAcute myeloid leukemiaClonal chromosomal abnormalitiesOligonucleotide array comparative genomic hybridizationGene contentBAC clonesEvidence-based approachComparative genomic hybridizationElderly patientsGenomic analysisGenomic contentDerivative chromosome 6Genomic featuresIsodicentric X chromosomeMyelodysplastic syndromeX chromosomeMyeloid leukemiaConclusionsOur dataCytogenomic analysisChromosome 6Clinical validitySegmental amplificationMYC geneClonal abnormalities