Article
Loss of glucocorticoid receptor expression mediates in vivo dexamethasone resistance in T-cell acute lymphoblastic leukemia.
Leukemia - 1 Aug 2020
Wandler Anica M, Huang Benjamin J, Craig Jeffrey W, Hayes Kathryn, Yan Hannah, Meyer Lauren K, Scacchetti Alessandro, Monsalve Gabriela, Dail Monique, Li Qing, Wong Jasmine C, Weinberg Olga, Hasserjian Robert P, Kogan Scott C, Jonsson Philip, Yamamoto Keith, Sampath Deepak, Nakitandwe Joy, Downing James R, Zhang Jinghui, Aster Jon C, Taylor Barry S, Shannon Kevin
Abstract excerpt
Despite decades of clinical use, mechanisms of glucocorticoid resistance are poorly understood. We treated primary murine T lineage acute lymphoblastic leukemias (T-ALLs) with the glucocorticoid dexamethasone (DEX) alone and in combination with the pan-PI3 kinase inhibitor GDC-0941 and observed a robust response to DEX that was modestly enhanced by GDC-0941. Continuous in vivo treatment invariably resulted in...
Topics
- Animals
- Dexamethasone
- Drug Resistance, Neoplasm
- Humans
- Indazoles
- Male
- Mice
- Mice, Inbred C57BL
- Mutation