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

Clara RegleroChelsea L DieckArie ZaskFarhad ForouharAnouchka P LaurentWen-Hsuan Wendy LinRobert AlberoHannah I MillerCindy MaJulie M Gastier-FosterMignon L LohLiang TongBrent R StockwellTeresa PalomeroAdolfo A Ferrando
Published in: Cancer discovery (2022)
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.
Keyphrases
  • acute lymphoblastic leukemia
  • genome wide
  • deep learning
  • allogeneic hematopoietic stem cell transplantation
  • dna methylation
  • squamous cell carcinoma
  • gene expression
  • locally advanced
  • acute myeloid leukemia