Genetics and mechanisms of NT5C2-driven chemotherapy resistance in relapsed ALL.
Blood
; 133(21): 2263-2268, 2019 05 23.
Article
en En
| MEDLINE
| ID: mdl-30910786
ABSTRACT
Mutations in the cytosolic 5' nucleotidase II (NT5C2) gene drive resistance to thiopurine chemotherapy in relapsed acute lymphoblastic leukemia (ALL). Mechanistically, NT5C2 mutant proteins have increased nucleotidase activity as a result of altered activating and autoregulatory switch-off mechanisms. Leukemias with NT5C2 mutations are chemoresistant to 6-mercaptopurine yet show impaired proliferation and self-renewal. Direct targeting of NT5C2 or inhibition of compensatory pathways active in NT5C2 mutant cells may antagonize the emergence of NT5C2 mutant clones driving resistance and relapse in ALL.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
5'-Nucleotidasa
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Proliferación Celular
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Mercaptopurina
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Mutación
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Proteínas de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2019
Tipo del documento:
Article