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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533602 | PMC |
| http://dx.doi.org/10.1182/blood-2019-01-852392 | DOI Listing |
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