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Genetics and mechanisms of NT5C2-driven chemotherapy resistance in relapsed ALL.

著者 Dieck CL , Ferrando AA
Blood.2019 Mar 25 ; ():.
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Mutations in the cytosolic 5' nucleotidase II () 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. Leukemia cells harboring activating mutations are chemo-resistant to 6-mercaptopurine (6-MP), yet show impaired proliferative and self-renewal capacity. Direct inhibition of NT5C2 or pharmacologic targeting of compensatory pathways active in mutant cells may antagonize the emergence of mutant clones driving resistance and relapse in ALL.
PMID: 30910786 [PubMed - as supplied by publisher]
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