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
2016
Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells
Sun B, Fiskus W, Zhang L, Raina K, Coleman K, Winkler J, Qian Y, Crew A, Shen A, Saenz D, Mill C, Wang M, Crews C, Bhalla K. Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells. Blood 2016, 128: 1058. DOI: 10.1182/blood.v128.22.1058.1058.Peer-Reviewed Original ResearchTarget gene expressionBruton's tyrosine kinaseC-MycARV-825Transcription factorsPrimary MCL cellsTranscriptional activityGene expressionTyrosine kinaseBcl-xLE3 ubiquitin ligase activityMCL cellsUbiquitin ligase activityHuman mantle cell lymphoma cellsB-cell receptor signalingCell receptor signalingBinding of BRD4Regulation of mRNAInk4a/ArfAcetylated chromatinCopy number gainsLigase activityHematopoietic progenitor cellsBET proteinsBETi treatment