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Blood. 2019 May 23;133(21):2263-2268. doi: 10.1182/blood-2019-01-852392. Epub 2019 Mar 25.

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

Author information

1
Institute for Cancer Genetics and.
2
Department of Systems Biology, Columbia University, New York, NY; and.
3
Department of Pediatrics and.
4
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY.

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.

PMID:
30910786
PMCID:
PMC6533602
[Available on 2020-05-23]
DOI:
10.1182/blood-2019-01-852392

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