2025
FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia
Huang H, Li X, Luo J, Gao C, Yang M, Xu J, Xie T, Chen Z, Wang D, Wang Y, Li H, Huang J, Liu Y, Zhang H, Ntziachristos P, Zhao Y, Qing G, Liu H. FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia. Science Advances 2025, 11: eadq3052. PMID: 40435251, PMCID: PMC12118595, DOI: 10.1126/sciadv.adq3052.Peer-Reviewed Original ResearchConceptsT-cell leukemiaT-ALLT-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaExpression of glycolytic genesDevelopment of potential therapeutic strategiesPotential therapeutic strategyAntileukemia efficacyLymphoblastic leukemiaLeukemia initiationLymphoid leukemiaTherapeutic strategiesGlycolytic genesPharmacological inhibitionMetabolic rewiringLeukemiaDemethylase FTOHuman cancersN6-methyladenosineMRNA stabilityTherapeutic targetCancerMechanistic analysisMRNAModel system
2024
A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B‐cell or T‐cell acute lymphoblastic leukemia: Results from the ECOG‐ACRIN EA9152 protocol
Palmisiano N, Lee J, Claxton D, Paietta E, Alkhateeb H, Park J, Podoltsev N, Atallah E, Schaar D, Dinner S, Webster J, Luger S, Litzow M. A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B‐cell or T‐cell acute lymphoblastic leukemia: Results from the ECOG‐ACRIN EA9152 protocol. EJHaem 2024, 5: 951-956. PMID: 39415930, PMCID: PMC11474352, DOI: 10.1002/jha2.991.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaMaximum tolerated doseT-cell acute lymphoblastic leukemiaLymphoblastic lymphomaLymphoblastic leukemiaTreatment-related adverse eventsDose level 3MRD-negative responseDose level 2Dose-limiting toxicityPhase I portionDose-escalation designPhase I/II trialPhase 1 trialPhase I objectivesPhase 2 portionAcute lymphoblastic leukemia subjectsEscalation designTolerated doseLiposomal vincristinePreclinical dataTherapeutic challengeEfficacy outcomesT cellsT-ALL
2023
Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress
Melnick A, Mullin C, Lin K, McCarter A, Liang S, Liu Y, Wang Q, Jerome N, Choe E, Kunnath N, Bodanapu G, Akter F, Magnuson B, Kumar S, Lombard D, Muntean A, Ljungman M, Sekiguchi J, Ryan R, Chiang M. Cdc73 protects Notch-induced T-cell leukemia cells from DNA damage and mitochondrial stress. Blood 2023, 142: 2159-2174. PMID: 37616559, PMCID: PMC10733839, DOI: 10.1182/blood.2023020144.Peer-Reviewed Original ResearchConceptsT-cell acute lymphoblastic leukemiaNotch signalingActivate transcription of genesExpression programsDNA damageTranscription of genesT-ALL oncogenesTranscription factor ETS1Elevated Notch signalingT-cell leukemia cellsImpaired mitochondrial functionGene expression profilesGene expression programsT cell developmentTranscription machineryActivate transcriptionActivate Notch signalingMitochondrial stressOncogenic NotchTargeting Notch signalingOxidative phosphorylationActivate expressionDNA repairMitochondrial functionNotch complex
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, PMCID: PMC12002038, 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
2020
Combinatorial ETS1-Dependent Control of Oncogenic NOTCH1 Enhancers in T-cell LeukemiaETS1-Dependent Control of Notch Transcriptional Programs
McCarter A, Della Gatta G, Melnick A, Kim E, Sha C, Wang Q, Nalamolu J, Liu Y, Keeley T, Yan R, Sun M, Kodgule R, Kunnath N, Ambesi-Impiombato A, Kuick R, Rao A, Ryan R, Kee B, Samuelson L, Ostrowski M, Ferrando A, Chiang M. Combinatorial ETS1-Dependent Control of Oncogenic NOTCH1 Enhancers in T-cell LeukemiaETS1-Dependent Control of Notch Transcriptional Programs. Blood Cancer Discovery 2020, 1: 178-197. PMID: 32924017, PMCID: PMC7482717, DOI: 10.1158/2643-3230.bcd-20-0026.Peer-Reviewed Original ResearchConceptsT-cell acute lymphoblastic leukemiaPan-Notch inhibitorsT cellsNotch-responsive elementsT cell developmentTranscription complexGenetic approachesTranscriptional elementsT-cell transcription factorsTranscription factorsTranscriptional programsAnti-Notch therapiesResponse elementNotch activationAcute lymphoblastic leukemiaEffector pathwaysETS1Lymphoblastic leukemiaProfiling studiesIntestinal toxicityMouse modelIntestinal effectsTreat cancerAdverse effectsSuppressive effect
2017
BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825 Targets Both NOTCH1-MYC Regulatory Circuit and Leukemia-Microenvironment in T-ALL
Piya S, Mu H, Bhattacharya S, McQueen T, Davis R, Ruvolo V, Baran N, Qian Y, Raina K, Crews C, You M, McKay P, Konopleva M, Kantarjian H, Andreeff M, Borthakur G. BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825 Targets Both NOTCH1-MYC Regulatory Circuit and Leukemia-Microenvironment in T-ALL. Blood 2017, 130: 716. DOI: 10.1182/blood.v130.suppl_1.716.716.Peer-Reviewed Original ResearchT-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaLymphoblastic leukemiaARV-825PI3K/AktGamma-secretase inhibitorsMouse modelRelapsed T-cell acute lymphoblastic leukemiaVehicle-treated control micePatient-derived xenograft mouse modelsCell linesLow leukemia burdenCell acute lymphoblastic leukemiaReactive oxygen speciesT-cell lymphoblastic leukemiaAnti-leukemic effectsXenograft mouse modelLeukemia-stroma interactionsPDX mouse modelsBristol-Meyers SquibbG1/S cell cycle progressionPersistence of diseaseAttractive therapeutic targetIntra-cellular reactive oxygen speciesMicroenvironmental signals
2016
Facial manifestations of Epstein–Barr virus‐related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations
Lu B, Kojima L, Huang M, Friedmann A, Ferry J, Weinstein H. Facial manifestations of Epstein–Barr virus‐related lymphoproliferative disease in childhood acute lymphoblastic leukemia in remission: Two atypical presentations. Pediatric Blood & Cancer 2016, 63: 2042-2045. PMID: 27392033, DOI: 10.1002/pbc.26102.Peer-Reviewed Case Reports and Technical NotesConceptsAcute lymphoblastic leukemiaLymphoblastic leukemiaLymphoproliferative diseaseB-cell acute lymphoblastic leukemiaRight-sided facial swellingT-cell acute lymphoblastic leukemiaChildhood acute lymphoblastic leukemiaHematopoietic transplantationMaintenance chemotherapyPrimary immunodeficiencyBilateral dacryoadenitisAtypical presentationFacial swellingLip lesionsNeither patientLymphoplasmacytic infiltrationT cellsFacial manifestationsFacial lesionsB cellsPatientsDe-EscalationRemissionLeukemiaLesions
2015
The PIAS-like Coactivator Zmiz1 Is a Direct and Selective Cofactor of Notch1 in T Cell Development and Leukemia
Pinnell N, Yan R, Cho H, Keeley T, Murai M, Liu Y, Alarcon A, Qin J, Wang Q, Kuick R, Elenitoba-Johnson K, Maillard I, Samuelson L, Cierpicki T, Chiang M. The PIAS-like Coactivator Zmiz1 Is a Direct and Selective Cofactor of Notch1 in T Cell Development and Leukemia. Immunity 2015, 43: 870-883. PMID: 26522984, PMCID: PMC4654973, DOI: 10.1016/j.immuni.2015.10.007.Peer-Reviewed Original ResearchConceptsT cell developmentIntestinal homeostasisNotch target genesT-ALLT-cell acute lymphoblastic leukemiaCell acute lymphoblastic leukemiaZMIZ1Pan-Notch inhibitorsTarget genesAcute lymphoblastic leukemiaCell developmentTumor suppressorCo-expressionNotch signalingActive Notch1Promote cancerMyeloid suppressionLymphoblastic leukemiaNotch1Leukemic growthNotch inhibitorClinical trialsHomeostasisLeukemiaInhibitorsTransplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research
Burke M, Verneris M, Le Rademacher J, He W, Abdel-Azim H, Abraham A, Auletta J, Ayas M, Brown V, Cairo M, Chan K, Diaz Perez M, Dvorak C, Egeler R, Eldjerou L, Frangoul H, Guilcher G, Hayashi R, Ibrahim A, Kasow K, Leung W, Olsson R, Pulsipher M, Shah N, Shah N, Thiel E, Talano J, Kitko C. Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research. Transplantation And Cellular Therapy 2015, 21: 2154-2159. PMID: 26327632, PMCID: PMC4654112, DOI: 10.1016/j.bbmt.2015.08.023.Peer-Reviewed Original ResearchMeSH KeywordsAcademic Medical CentersAcute DiseaseAdolescentBone Marrow TransplantationChildChild, PreschoolChronic DiseaseFemaleGraft vs Host DiseaseHumansImmunosuppressive AgentsInternational CooperationMaleMyeloablative AgonistsPrecursor T-Cell Lymphoblastic Leukemia-LymphomaProspective StudiesRecurrenceRemission InductionSeverity of Illness IndexSurvival AnalysisTransplantation ConditioningTransplantation, HomologousTreatment OutcomeConceptsHematopoietic cell transplantationT-cell acute lymphoblastic leukemiaCell acute lymphoblastic leukemiaMarrow Transplant ResearchAcute lymphoblastic leukemiaInternational BloodLymphoblastic leukemiaTransplant ResearchRelapsed T-cell acute lymphoblastic leukemiaThree-year overall survivalAllogeneic hematopoietic cell transplantationDisease-free survival ratesBone marrow/peripheral bloodTransplant-related mortalitySecond complete remissionBone marrow relapseUmbilical cord bloodPediatric T-ALLChronic graftExtramedullary relapseSecond remissionComplete remissionExtramedullary diseaseHost diseaseMarrow relapseStructure of the ABL2/ARG kinase in complex with dasatinib
Ha BH, Simpson MA, Koleske AJ, Boggon TJ. Structure of the ABL2/ARG kinase in complex with dasatinib. Acta Crystallographica Section F: Structural Biology Communications 2015, 71: 443-8. PMID: 25849507, PMCID: PMC4388181, DOI: 10.1107/s2053230x15004793.Peer-Reviewed Original ResearchConceptsT-cell acute lymphoblastic leukemiaActivation loop tyrosinesABL kinase activationGlycine-rich P-loopCell morphogenesisCo-crystal structureBreakpoint cluster regionCellular functionsArg genesCatalytic domainAbl familyArg kinaseP-loopKinase activationBiological roleOpen conformationTyrosine kinaseAbl kinaseKinaseGenesKinase inhibitorsABL1 geneArgCluster regionTyrosine kinase inhibitors
2014
PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells
Shojaee S, Cazzaniga V, Schjerven H, Buchner M, Hurtz C, Geng H, Hochhaus A, Cazzaniga G, Melnick A, Kornblau S, Graeber T, Muschen M. PTEN Is Essential for Normal Cytokine Signaling and Oncogenic Transformation of Pre-B Cells. Blood 2014, 124: 262. DOI: 10.1182/blood.v124.21.262.262.Peer-Reviewed Original ResearchAcute lymphoblastic leukemiaAlleles of PTENDeletion of PTENPI3K-Akt pathwayPI3K-Akt signalingGlucocorticoid resistanceHuman preSmall molecule inhibitorsBCR-ABL1Expression levelsMyeloid lineage leukemiasPatient-derived prePTEN deletionT-cell acute lymphoblastic leukemiaCell acute lymphoblastic leukemiaHigh expression levelsLeukemia cellsTime of diagnosisPoor clinical outcomeCell deathMature B-cell lymphomasPTEN inhibitionHuman cancersLeukemia/lymphomaB-cell lymphoma
2013
A 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia
Goodwin JE, Palmer M, Pashankar F, Tufro A, Moeckel G. A 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia. Clinical Nephrology 2013, 82: 205-210. PMID: 23391318, PMCID: PMC6990651, DOI: 10.5414/cn107767.Peer-Reviewed Original ResearchConceptsStem cell transplantHematopoietic stem cell transplantCell transplantRenal insufficiencyKidney biopsyPediatric patientsNephrotic syndromeExtensive foot process effacementAbnormal lymphocyte responsesT-cell acute lymphoblastic leukemiaChronic kidney diseaseChronic interstitial nephritisAcute lymphoblastic leukemiaPre-conditioning regimensFoot process effacementHost diseaseImmunosuppressive therapyRenal failureInterstitial nephritisLymphocyte responsesCommon sequelaeInterstitial infiltratesProphylactic medicationKidney diseaseLikely multifactorial
2012
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Tautz L, Sergienko E, Xu J, Liu W, Dahl R, Critton D, Su Y, Brown B, Chan X, Yang L, Bobkova E, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford N, Chung T, Mustelin T, Page R, Lombroso P. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. The FASEB Journal 2012, 26: 766.12-766.12. DOI: 10.1096/fasebj.26.1_supplement.766.12.Peer-Reviewed Original ResearchHematopoietic protein tyrosine phosphataseP38 activationProtein tyrosine phosphataseUnique amino acid residuesAmino acid residuesNew drug targetsCell cycle arrestMAP kinases ERK1/2Activation of ERK1/2Tyrosine phosphataseHePTPMutagenesis experimentsMAP kinaseKinases ERK1/2Acid residuesCatalytic pocketDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaERK1/2Prolonged activationHuman T cellsPharmacological inhibitionCancer cells
2011
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Sergienko E, Xu J, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. ACS Chemical Biology 2011, 7: 367-377. PMID: 22070201, PMCID: PMC3288537, DOI: 10.1021/cb2004274.Peer-Reviewed Original ResearchConceptsHematopoietic protein tyrosine phosphataseP38 activationMitogen-activated protein kinases ERK1/2Protein tyrosine phosphataseUnique amino acid residuesSmall molecule modulatorsProtein kinases ERK1/2Amino acid residuesRegulation of MAPKNew drug targetsCell cycle arrestTyrosine phosphataseHePTPMutagenesis experimentsKinases ERK1/2Acid residuesCatalytic pocketCell senescenceDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaHematopoietic cellsERK1/2Prolonged activation
2006
Acute renal failure from xanthine nephropathy during management of acute leukemia
LaRosa C, McMullen L, Bakdash S, Ellis D, Krishnamurti L, Wu H, Moritz M. Acute renal failure from xanthine nephropathy during management of acute leukemia. Pediatric Nephrology 2006, 22: 132-135. PMID: 17039332, DOI: 10.1007/s00467-006-0287-z.Peer-Reviewed Original ResearchConceptsTumor lysis syndromeAcute renal failureLysis syndromeXanthine nephropathyRenal failureTumor lysis syndrome prophylaxisOliguric acute renal failureT-cell acute lymphoblastic leukemiaLife-threatening complicationsAcute lymphoblastic leukemiaDiagnosis of patientsAggressive chemotherapyInduction chemotherapyUrinary xanthineUrine alkalinizationSerious complicationsLymphoproliferative malignanciesLymphoblastic leukemiaAcute leukemiaUrine measurementsPreemptive useNephropathyUric acid synthesisSyndromeHypoxanthine levels
2004
Sil overexpression in lung cancer characterizes tumors with increased mitotic activity
Erez A, Perelman M, Hewitt SM, Cojacaru G, Goldberg I, Shahar I, Yaron P, Muler I, Campaner S, Amariglio N, Rechavi G, Kirsch IR, Krupsky M, Kaminski N, Izraeli S. Sil overexpression in lung cancer characterizes tumors with increased mitotic activity. Oncogene 2004, 23: 5371-5377. PMID: 15107824, DOI: 10.1038/sj.onc.1207685.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaBlotting, WesternCell DifferentiationCell DivisionCell LineG1 PhaseGenes, Immediate-EarlyHeLa CellsHumansImmunohistochemistryIntracellular Signaling Peptides and ProteinsKinetochoresLung NeoplasmsMitosisNeoplasm MetastasisOligonucleotide Array Sequence AnalysisOncogene Proteins, FusionRNA, MessengerConceptsLung cancerT-cell acute lymphoblastic leukemiaMitotic activityAcute lymphoblastic leukemiaLung cancer samplesPrimary adenocarcinomaLymphoblastic leukemiaMetastatic spreadImmediate early genesMicroarray gene expression analysisTissue arraysPeak levelsCancer samplesProtein expressionTumorsCancerProtein levelsCell proliferationMitotic indexCommon chromosomal rearrangementsGene expression analysisSIL geneEarly genesOverexpressionRecent studies
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