Glucocorticoids and selumetinib are highly synergistic in RAS pathway mutated childhood acute lymphoblastic leukemia through upregulation of BIM

Autor: Helen J. Blair, Rosanna K. Jackson, Chris Halsey, Elizabeth Matheson, Gareth J. Veal, Huw D. Thomas, David R. Newell, Dino Masic, Julie Irving, Marian Case, Josef Vormoor
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Haematologica
ISSN: 0390-6078
Popis: New drugs are needed for the treatment of relapsed acute lymphoblastic leukemia and preclinical evaluation of the MEK inhibitor, selumetinib, has shown that this drug has excellent activity in those leukemias with RAS pathway mutations. The proapoptotic protein, BIM is pivotal in the induction of cell death by both selumetinib and glucocorticoids, suggesting the potential for synergy. Thus, combination indices for dexamethasone and selumetinib were determined in RAS pathway-mutated acute lymphoblastic leukemia primagraft cells in vitro and were indicative of strong synergism (combination index
Databáze: OpenAIRE