Aberrant GSK3ß nuclear localization promotes AML growth and drug resistance.
Blood Adv
; 2(21): 2890-2903, 2018 11 13.
Article
en 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
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Núcleo Celular
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Resistencia a Antineoplásicos
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Proliferación Celular
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Glucógeno Sintasa Quinasa 3 beta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Blood Adv
Año:
2018
Tipo del documento:
Article