Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance.
Pharmacogenomics J
; 18(3): 467-473, 2018 05 22.
Article
de En
| MEDLINE
| ID: mdl-29205205
ABSTRACT
Elucidating resistance mechanisms for therapeutic monoclonal antibodies (MAbs) is challenging, because they are difficult to study in non-human models. We therefore developed a strategy to genetically map in vitro drug sensitivity, identifying genes that alter responsiveness to rituximab, a therapeutic anti-CD20 MAb that provides significant benefit to patients with B-cell malignancies. We discovered novel loci with genome-wide mapping analyses and functionally validated one of these genes, CBLB, which causes rituximab resistance when knocked down in lymphoma cells. This study demonstrates the utility of genome-wide mapping to discover novel biological mechanisms of potential clinical advantage.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Leucémie chronique lymphocytaire à cellules B
/
Résistance aux médicaments antinéoplasiques
/
Protéines adaptatrices de la transduction du signal
/
Protéines proto-oncogènes c-cbl
/
Rituximab
Limites:
Female
/
Humans
/
Male
Langue:
En
Journal:
Pharmacogenomics J
Sujet du journal:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique