Genetics and Mechanisms of NT5C2-driven Chemotherapy Resistance in Relapsed ALL

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2019 Mar 27

PMID 30910786

Citations 21

Authors

Chelsea L Dieck

Adolfo Ferrando

Affiliations

Soon will be listed here.

Abstract

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. Leukemias with mutations are chemoresistant to 6-mercaptopurine yet show impaired proliferation and self-renewal. Direct targeting of NT5C2 or inhibition of compensatory pathways active in mutant cells may antagonize the emergence of mutant clones driving resistance and relapse in ALL.

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