Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia.

Clara Reglero,Chelsea L Dieck,Arie Zask,Farhad Forouhar,Anouchka P Laurent,Wen-Hsuan W Lin,Robert Albero,Hannah I Miller, Cindy Ma,Julie M Gastier-Foster,Mignon L Loh,Liang Tong,Brent R Stockwell,Teresa Palomero,Adolfo A Ferrando

Cancer discovery（2022）

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摘要

Relapse-associated NT5C2 mutations directly contribute to relapse in ALL by driving resistance to chemotherapy with 6-MP. Pharmacologic inhibition of NT5C2 with CRCD2, a first-in-class nucleotidase inhibitor, enhances the cytotoxic effects of 6-MP and effectively reverses thiopurine resistance mediated by genetic and nongenetic mechanisms of NT5C2 activation in ALL. This article is highlighted in the In This Issue feature, p. 2483.

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nt5c2 reverses genetic,leukemia

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