Transporter-mediated protection against thiopurine-induced hematopoietic toxicity.

  title={Transporter-mediated protection against thiopurine-induced hematopoietic toxicity.},
  author={Partha Krishnamurthy and Matthias Schwab and Kazumasa Takenaka and Deepa Nachagari and Jessica Morgan and Mark Leslie and Weinan Du and Kelli Boyd and Meyling Cheok and Hiromitsu Nakauchi and Catia Marzolini and Richard B Kim and Balasubramanian Poonkuzhali and Erin G. Schuetz and William Evans and Mary Relling and John D. Schuetz},
  journal={Cancer research},
  volume={68 13},
Thiopurines are effective immunosuppressants and anticancer agents, but intracellular accumulation of their active metabolites (6-thioguanine nucleotides, 6-TGN) causes dose-limiting hematopoietic toxicity. Thiopurine S-methyltransferase deficiency is known to exacerbate thiopurine toxicity. However, many patients are highly sensitive to thiopurines for unknown reasons. We show that multidrug-resistance protein 4 (Mrp4) is abundant in myeloid progenitors and tested the role of the Mrp4, an ATP… CONTINUE READING


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