2017
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells
Sun B, Fiskus W, Qian Y, Rajapakshe K, Raina K, Coleman KG, Crew AP, Shen A, Saenz DT, Mill CP, Nowak AJ, Jain N, Zhang L, Wang M, Khoury JD, Coarfa C, Crews CM, Bhalla KN. BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells. Leukemia 2017, 32: 343-352. PMID: 28663582, DOI: 10.1038/leu.2017.207.Peer-Reviewed Original ResearchConceptsMantle cell lymphoma cellsMCL cellsCell lymphoma cellsARV-825ARV-771Lymphoma cellsGreater survival improvementSuperior preclinical activityCDK4/6 inhibitor palbociclibNuclear factor-κB (NF-κB) target genesExtraterminal protein inhibitorSurvival improvementInhibitor palbociclibPreclinical activityCDKN1A/p21Inhibitor treatmentSuperior pharmacological propertiesVivo growthCyclin D1Pharmacological propertiesProtein expressionMore apoptosisVivo evaluationIncomplete inhibitionC-Myc
2016
Superior Lethal Activity of Novel BET Protein Proteolysis Targeting Chimera (BETP-PROTACs) Versus Betp Bromodomain Inhibitor (BETi) Against Post-Myeloproliferative Neoplasm (MPN) Secondary (s) AML Cells
Saenz D, Fiskus W, Raina K, Manshouri T, Coleman K, Winkler J, Qian Y, Crew A, Shen A, Mill C, Sun B, Verstovsek S, Crews C, Bhalla K. Superior Lethal Activity of Novel BET Protein Proteolysis Targeting Chimera (BETP-PROTACs) Versus Betp Bromodomain Inhibitor (BETi) Against Post-Myeloproliferative Neoplasm (MPN) Secondary (s) AML Cells. Blood 2016, 128: 747. DOI: 10.1182/blood.v128.22.747.747.Peer-Reviewed Original ResearchTyk2 tyrosine kinaseMPN-MFARV-825Stem/progenitor cellsHEL92.1.7 cellsHematopoietic stem/progenitor cellsProgenitor cellsC-MycP-STAT5ARV-771BETi treatmentMass cytometry approachProtein expressionLoss of responseNormal hematopoietic progenitor cellsNotable clinical benefitJAK-STATProtein array analysisNegative myeloproliferative neoplasmsBcl-xLMedian survivalClinical outcomesClinical benefitHematopoietic progenitor cellsWestern analysis