Glucocorticoids and selumetinib are highly synergistic in RAS pathway-mutated childhood acute lymphoblastic leukemia through upregulation of BIM.
Adolescent
Animals
Bcl-2-Like Protein 11
/ metabolism
Benzimidazoles
/ administration & dosage
Child
Child, Preschool
DNA Mutational Analysis
Dexamethasone
/ administration & dosage
Drug Synergism
Female
Glucocorticoids
/ administration & dosage
Humans
Male
Mice
Mice, Inbred NOD
Mice, SCID
Mutation
Neoplasm Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Up-Regulation
ras Proteins
/ genetics
Journal
Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
16
03
2018
accepted:
15
01
2019
pubmed:
19
1
2019
medline:
29
7
2020
entrez:
19
1
2019
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 30655370
pii: haematol.2017.185975
doi: 10.3324/haematol.2017.185975
pmc: PMC6717586
doi:
Substances chimiques
AZD 6244
0
BCL2L11 protein, human
0
Bcl-2-Like Protein 11
0
Benzimidazoles
0
Glucocorticoids
0
Dexamethasone
7S5I7G3JQL
ras Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1804-1811Subventions
Organisme : Blood Cancer UK
ID : 11007
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12788
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ETM/374
Pays : United Kingdom
Informations de copyright
Copyright© 2019 Ferrata Storti Foundation.
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