Aberrant GSK3ß nuclear localization promotes AML growth and drug resistance.
Blood Adv
; 2(21): 2890-2903, 2018 11 13.
Article
em En
| MEDLINE
| ID: mdl-30385433
ABSTRACT
Acute myeloid leukemia (AML) is a devastating disease with poor patient survival. As targetable mutations in AML are rare, novel oncogenic mechanisms are needed to define new therapeutic targets. We identified AML cells that exhibit an aberrant pool of nuclear glycogen synthase kinase 3ß (GSK3ß). This nuclear fraction drives AML growth and drug resistance. Nuclear, but not cytoplasmic, GSK3ß enhances AML colony formation and AML growth in mouse models. Nuclear GSK3ß drives AML partially by promoting nuclear localization of the NF-κB subunit, p65. Finally, nuclear GSK3ß localization has clinical significance as it strongly correlates to worse patient survival (n = 86; hazard ratio = 2.2; P < .01) and mediates drug resistance in cell and animal models. Nuclear localization of GSK3ß may define a novel oncogenic mechanism in AML and represent a new therapeutic target.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Núcleo Celular
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Resistencia a Medicamentos Antineoplásicos
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Proliferação de Células
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Glicogênio Sintase Quinase 3 beta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article