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