2024
Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant stateThe FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export
Olazabal-Herrero A, He B, Kwon Y, Gupta A, Dutta A, Huang Y, Boddu P, Liang Z, Liang F, Teng Y, Lan L, Chen X, Pei H, Pillai M, Sung P, Kupfer G. The FANCI/FANCD2 complex links DNA damage response to R-loop regulation through SRSF1-mediated mRNA export. Cell Reports 2024, 43: 113610. PMID: 38165804, PMCID: PMC10865995, DOI: 10.1016/j.celrep.2023.113610.Peer-Reviewed Original Research
2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kineticsTranscription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape
Boddu P, Gupta A, Roy R, Herrero A, Verma A, Neugebauer K, Pillai M. Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape. Blood 2023, 142: 709. DOI: 10.1182/blood-2023-188083.Peer-Reviewed Original ResearchChromatin organizationSuch epigenetic changesGenome editing approachesRNA splicing factorsChromatin landscapeSingle mutant alleleEpigenetic landscapeGenomic integrityTranscription defectTranscription kineticsSplicing factorsChIP-seqEpigenetic regulatorsEpigenetic changesEpigenetic therapyMutant allelesEditing approachesFactor mutationsK562 cell lineDownstream effectsCell linesMyeloid disordersClonal myeloid disordersHDAC pathwayMutations
2022
A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies
Boddu P, Senapati J, Ravandi‐Kashani F, Jabbour E, Jain N, Ayres M, Chen Y, Keating M, Kantarjian H, Gandhi V, Kadia T. A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. Cancer 2022, 129: 580-589. PMID: 36448227, DOI: 10.1002/cncr.34570.Peer-Reviewed Original ResearchConceptsPhase 1 studyT-cell prolymphocytic leukemiaComplete remissionContinuous infusionRefractory T-cell acute lymphoblastic leukemiaCentral nervous system toxicityIncomplete platelet recoveryRefractory lymphoid malignanciesT-cell acute lymphoblastic leukemiaUse of nelarabineFavorable clinical responseNervous system toxicityOverall response rateContinuous infusion scheduleAcute lymphoblastic leukemiaClinical responseCentral neurotoxicityLymphoblastic lymphomaMedian agePeripheral neuropathyInfusion scheduleSafety profilePatient populationLymphoblastic leukemiaPlatelet recovery
2021
Generation of scalable cancer models by combining AAV-intron-trap, CRISPR/Cas9, and inducible Cre-recombinase
Boddu PC, Gupta AK, Kim JS, Neugebauer KM, Waldman T, Pillai MM. Generation of scalable cancer models by combining AAV-intron-trap, CRISPR/Cas9, and inducible Cre-recombinase. Communications Biology 2021, 4: 1184. PMID: 34645977, PMCID: PMC8514589, DOI: 10.1038/s42003-021-02690-1.Peer-Reviewed Original Research40008 COMBINED CRISPR/CAS9 AND AAV FOR THE GENERATION OF CONDITIONAL ISOGENIC GENE KNOCK-INS
Boddu P, Gupta A, Waldman T, Pillai M. 40008 COMBINED CRISPR/CAS9 AND AAV FOR THE GENERATION OF CONDITIONAL ISOGENIC GENE KNOCK-INS. Journal Of Clinical And Translational Science 2021, 5: 22-22. PMCID: PMC8827824, DOI: 10.1017/cts.2021.460.Peer-Reviewed Original ResearchDistinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications
Kim ST, Sheshadri A, Shannon V, Kontoyiannis DP, Kantarjian H, Garcia-Manero G, Ravandi F, Im JS, Boddu P, Bashoura L, Balachandran DD, Evans SE, Faiz S, Vazquez W, Divenko M, Mathur R, Tippen SP, Gumbs C, Neelapu SS, Naing A, Wang L, Diab A, Futreal A, Nurieva R, Daver N. Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications. Frontiers In Immunology 2021, 11: 590494. PMID: 33552049, PMCID: PMC7859512, DOI: 10.3389/fimmu.2020.590494.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsAML/MDS patientsPulmonary complicationsAcute myeloid leukemiaMDS patientsICI groupCheckpoint inhibitorsBronchoalveolar lavageMyelodysplastic syndromeT cellsTh17/Th1 cellsBAL T cellsRisk of pneumonitisBronchoalveolar lavage fluidFungal pneumoniaPulmonary symptomsIL-17Lavage fluidPeripheral bloodTh1 cellsLeukemia patientsMyeloid leukemiaDistinct immunophenotypePatientsComplications
2020
Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML)
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-1 Trial: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease in Acute Myeloid Leukemia (AML) 1- an Investigator-Initiated, CTEP-Sponsored, Randomized Phase 2 Study of the Anti-PD-1 Antibody Pembrolizumab in Combination with Conventional Intensive Chemotherapy (IC) As Frontline Therapy in Patients with Acute Myeloid Leukemia (AML). Blood 2020, 136: 15. DOI: 10.1182/blood-2020-139668.Peer-Reviewed Original ResearchMRD-negative complete responsesAcute myeloid leukemiaMinimal residual diseaseEvent-free survivalImmune checkpoint inhibitionPhase 2 studyIntensive chemotherapyDuration of responseComplete responseOverall survivalPD-1AML patientsDay 1Free survivalHematologic improvementInitial treatmentStudy armsResidual diseaseDay IVLeukemia-specific T-cell responsesSingle-arm phase 2 studyPD-1/PD-L1 pathwayTherapy-related acute myeloid leukemiaCancer Therapy Evaluation ProgramImmune cell subsets analysisBlast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy
Zeidan A, Boddu P, Wood B, Zelterman D, Little R, Ivy S, Caldwell A, Sanchez-Espiridion B, Alatrash G, Sharon E, Radich J. Blast MRD AML-2: Blockade of PD-1 Added to Standard Therapy to Target Measurable Residual Disease (MDR) in Acute Myeloid Leukemia (AML) 2- a Randomized Phase 2 Study of the Venetoclax, Azacitidine, and Pembrolizumab Versus Venetoclax and Azacitidine As First Line Therapy in Older Patients with AML Who Are Ineligible or Who Refuse Intensive Chemotherapy. Blood 2020, 136: 11-12. DOI: 10.1182/blood-2020-139752.Peer-Reviewed Original ResearchEvent-free survivalDuration of responseMRD-negative CRIntensive chemotherapyOverall survivalDay 1Complete remissionFree survivalHematologic improvementOlder patientsSecondary AMLPD-1Study armsAML patientsInitial treatmentHematologic disordersLeukemia-specific T-cell responsesCancer Therapy Evaluation ProgramCR/complete remissionImmune cell subsets analysisRandomized phase 2 studyRandomized phase 2 trialRandomized phase II studyAllogeneic stem cell transplantBetter long-term clinical outcomesSpecial considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts
Zeidan AM, Boddu PC, Patnaik MM, Bewersdorf JP, Stahl M, Rampal RK, Shallis R, Steensma DP, Savona MR, Sekeres MA, Roboz GJ, DeAngelo DJ, Schuh AC, Padron E, Zeidner JF, Walter RB, Onida F, Fathi A, DeZern A, Hobbs G, Stein EM, Vyas P, Wei AH, Bowen DT, Montesinos P, Griffiths EA, Verma AK, Keyzner A, Bar-Natan M, Navada SC, Kremyanskaya M, Goldberg AD, Al-Kali A, Heaney ML, Nazha A, Salman H, Luger S, Pratz KW, Konig H, Komrokji R, Deininger M, Cirici BX, Bhatt VR, Silverman LR, Erba HP, Fenaux P, Platzbecker U, Santini V, Wang ES, Tallman MS, Stone RM, Mascarenhas J. Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts. The Lancet Haematology 2020, 7: e601-e612. PMID: 32563283, PMCID: PMC7302757, DOI: 10.1016/s2352-3026(20)30205-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute leukemiaMyeloid neoplasmsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2COVID-19 pandemicClinical trial participationSyndrome coronavirus 2Care of patientsPost-infection outcomesGlobal public health crisisHealth care infrastructureInternational expertsAdult patientsPublic health crisisSupportive careCoronavirus 2Trial participationHigh-income countriesOngoing COVID-19 pandemicGeneral populationPatientsHealth care environmentNeoplasmsLeukemia
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 cellsThe golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia
Shallis RM, Boddu PC, Bewersdorf JP, Zeidan AM. The golden age for patients in their golden years: The progressive upheaval of age and the treatment of newly-diagnosed acute myeloid leukemia. Blood Reviews 2019, 40: 100639. PMID: 31761380, DOI: 10.1016/j.blre.2019.100639.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInduction therapyAcute myeloid leukemia patientsMost acute myeloid leukemia (AML) patientsAML patients ageIntensive induction therapyLeukemic stem cell persistenceOptimal treatment modalityMyeloid leukemia patientsPatient-specific factorsAcute myeloid leukemiaAvailability of therapiesMedical comorbiditiesOlder patientsPatient ageIntensive therapyOrgan reserveTreatment algorithmEarly mortalityLongstanding recommendationsTreatment modalitiesSuch therapyLeukemia patientsMyeloid leukemiaPatientsTherapyGut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia
Galloway-Peña JR, Shi Y, Peterson CB, Sahasrabhojane P, Gopalakrishnan V, Brumlow CE, Daver NG, Alfayez M, Boddu PC, Khan A, Wargo JA, Do KA, Jenq RR, Kontoyiannis DP, Shelburne SA. Gut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia. Clinical Infectious Diseases 2019, 71: 63-71. PMID: 31436833, PMCID: PMC7312220, DOI: 10.1093/cid/ciz777.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaInduction chemotherapyNeutrophil recoveryInfectious complicationsAML patientsMyeloid leukemiaAcute myeloid leukemia induction chemotherapyGut microbiome signaturesInfectious risk stratificationHematologic malignancy patientsExtended spectrum βSubsequent infectious complicationsStrong independent predictorHigher baseline levelsInduction therapyInfectious outcomesMalignancy patientsCarbapenem useIndependent predictorsTransplant settingAntibiotic administrationClinical outcomesRisk stratificationStool samplesMicrobiome signaturesHedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia
Shallis RM, Bewersdorf JP, Boddu PC, Zeidan AM. Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia. Expert Review Of Anticancer Therapy 2019, 19: 717-729. PMID: 31422721, DOI: 10.1080/14737140.2019.1652095.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute myeloid leukemiaHh pathway inhibitorsMyeloid leukemiaSurvival of AMLPathway inhibitorHh pathwayPoor-risk diseaseHedgehog pathway inhibitionStem cellsCombination therapyClinical trialsFirst approvalTherapeutic strategiesTherapeutic targetPathway inhibitionHematopoietic stem cellsNeoplasm therapyOlder populationTherapyHedgehog pathwayFurther studiesLeukemiaNormal hematopoiesisAdult stem cellsInhibitorsSMAC mimetics as potential cancer therapeutics in myeloid malignancies
Boddu P, Carter BZ, Verstovsek S, Pemmaraju N. SMAC mimetics as potential cancer therapeutics in myeloid malignancies. British Journal Of Haematology 2019, 185: 219-231. PMID: 30836448, DOI: 10.1111/bjh.15829.Peer-Reviewed Original ResearchConceptsSmac mimeticsSmall-molecule Smac mimeticsSecond mitochondria-derived activatorEvasion of apoptosisPro-apoptotic proteinsPotential cancer therapeuticsMyeloid malignanciesIAP antagonismApoptosis proteinIAP expressionApoptosis thresholdDeath receptorsCaspase proteinsCell deathImmune check-point blockadeIAP activityReceptor tyrosine kinase inhibitorsCheck-point blockadeCancer therapeuticsEffect of chemotherapyDirect targetingProteinTumor necrosis factorFas ligandTyrosine kinase inhibitorsWhat are the most promising new agents in myelodysplastic syndromes?
Chandhok NS, Boddu PC, Gore SD, Prebet T. What are the most promising new agents in myelodysplastic syndromes? Current Opinion In Hematology 2019, 26: 77-87. PMID: 30632987, DOI: 10.1097/moh.0000000000000483.BooksConceptsMyelodysplastic syndromePromising new agentNew agentsAllogeneic hematopoietic stem cell transplantationManagement of MDSHigh-risk myelodysplastic syndromeHematopoietic stem cell transplantationRisk myelodysplastic syndromesLong-term remissionStem cell transplantationHigh-risk groupLow-risk groupGoal of therapyAcute myeloid leukemiaProgression of diseaseBone marrow failure syndromesGroup of disordersQuality of lifeMarrow failure syndromesTransfusion dependenceTherapeutic optionsTreatment optionsBcl-2 inhibitorsDisease prognosticationMyeloid leukemia
2016
Idiopathic granulomatous mastitis mimicking inflammatory breast carcinoma: What are the odds?
Zulfiqar B, Appalaneni U, Ahmed B, Hassan A, Boddu P, Carey A. Idiopathic granulomatous mastitis mimicking inflammatory breast carcinoma: What are the odds? IDCases 2016, 6: 83-84. PMID: 27790396, PMCID: PMC5081417, DOI: 10.1016/j.idcr.2016.10.006.Peer-Reviewed Original ResearchThe impact of diagnostic discrepancies in aortic dissection management
Hassan A, Zabad A, Candrasekaran M, Mohammed A, Mahmoud S, Boddu P. The impact of diagnostic discrepancies in aortic dissection management. International Journal Of Medical Research & Health Sciences 2016, 5: 107. DOI: 10.5958/2319-5886.2016.00023.0.Peer-Reviewed Original ResearchBaclofen-induced toxic encephalopathy in end-stage renal disease: should we be more careful?
Mohammed A, Hassan A, Boddu P. Baclofen-induced toxic encephalopathy in end-stage renal disease: should we be more careful? Asian Pacific Journal Of Health Sciences 2016, 3: 53-55. DOI: 10.21276/apjhs.2016.3.1.9.Peer-Reviewed Original Research