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

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.

SUBMITTER: Dieck CL

PROVIDER: S-EPMC6533602 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Dieck Chelsea L CL Ferrando Adolfo A

Blood 20190325 21

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 pathway ...[more]

PMID: 30910786

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