Targeting PI3K Signaling in Acute Lymphoblastic Leukemia.
Int J Mol Sci
; 20(2)2019 Jan 18.
Article
de En
| MEDLINE
| ID: mdl-30669372
ABSTRACT
Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR). Stromal cell protection of ALL cells has been shown to require active AKT. In chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT pathway is reported. A novel FDA-approved PI3Kδ inhibitor, CAL-101/idelalisib, leads to downregulation of p-AKT and increased apoptosis of CLL cells. Recently, two additional PI3K inhibitors have received FDA approval. As the PI3K/AKT pathway is also implicated in adhesion-mediated survival of ALL cells, PI3K inhibitors have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K in normal hematopoietic cells, and in ALL. We focus on summarizing targeting strategies of PI3K in ALL.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transduction du signal
/
Phosphatidylinositol 3-kinases
/
Leucémie-lymphome lymphoblastique à précurseurs B et T
/
Thérapie moléculaire ciblée
/
Antinéoplasiques
Type d'étude:
Diagnostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
Int J Mol Sci
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique