2021
BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Fiskus W, Mill CP, Perera D, Birdwell C, Deng Q, Yang H, Lara BH, Jain N, Burger J, Ferrajoli A, Davis JA, Saenz DT, Jin W, Coarfa C, Crews CM, Green MR, Khoury JD, Bhalla KN. BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma. Leukemia 2021, 35: 2621-2634. PMID: 33654205, PMCID: PMC8410602, DOI: 10.1038/s41375-021-01181-w.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBiomarkers, TumorBridged Bicyclo Compounds, HeterocyclicCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansLymphoma, Large B-Cell, DiffuseMicePiperidinesProteinsProteolysisSulfonamidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLarge B-cell lymphomaB-cell lymphomaRichter transformationBET protein inhibitorLymphoma burdenImproved survivalCombination therapyC-Myc levelsEffective therapyNovel therapiesCell lymphomaXenograft modelProtein inhibitorTherapyBET inhibitorsProtein expressionCLLGenetic alterationsLymphomaInhibitorsIRF4Single-cell RNA-seqHuman modelCRISPR knockoutCells
2017
Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells
Saenz DT, Fiskus W, Qian Y, Manshouri T, Rajapakshe K, Raina K, Coleman KG, Crew AP, Shen A, Mill CP, Sun B, Qiu P, Kadia TM, Pemmaraju N, DiNardo C, Kim MS, Nowak AJ, Coarfa C, Crews CM, Verstovsek S, Bhalla KN. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Leukemia 2017, 31: 1951-1961. PMID: 28042144, PMCID: PMC5537055, DOI: 10.1038/leu.2016.393.Peer-Reviewed Original ResearchConceptsBET protein inhibitorARV-825Messenger RNAReverse phase protein arrayPhase protein arrayRNA-seqHematopoietic progenitor cellsNormal hematopoietic progenitor cellsBET proteinsE3 ubiquitin ligase cereblonLevels of p21Extraterminal (BET) proteinsBcl-xLBromodomain inhibitorsC-MycJAK inhibitor ruxolitinibBRD4Protein arraysProgenitor cellsProtein expressionHEL92.1.7 cellsImproved survivalLeukemia burdenNSG miceProfound depletion