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

Overview

Journal Cancer Discov

Specialty Oncology

Date 2022 Aug 19

PMID 35984649

Authors

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

Affiliations

Soon will be listed here.

Abstract

Significance: 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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