Resistance revealed in acute lymphoblastic leukemia

The treatment of acute lymphoblastic leukemia (ALL) is one of the great success stories in oncology. However, patients who fail to achieve remission or relapse after chemotherapy continue to have a very poor prognosis, and the mechanisms underlying therapy failures are largely unknown. A new study suggests that gain-of-function mutations in NT5C2, a gene that encodes an enzyme that metabolizes chemotherapeutic drugs used against ALL, contribute to chemotherapy resistance (pages 368–371).

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Figure 1: Model of mutant NT5C2-mediated drug resistance.

References

  1. 1

    Huguet, F. et al. J. Clin. Oncol. 27, 911–918 (2009).

  2. 2

    Fielding, A.K. et al. Blood 109, 944–950 (2007).

  3. 3

    Ernst, T. & Hochhaus, A. Semin. Oncol. 39, 58–66 (2012).

  4. 4

    Poulikakos, P.I. & Rosen, N. Cancer Cell 19, 11–15 (2011).

  5. 5

    Tzoneza, G. et al. Nat. Med. 19, 368–371 (2013).

  6. 6

    Brouwer, C. et al. Clin. Chim. Acta 361, 95–103 (2005).

  7. 7

    Galmarini, C.M., Jordheim, L. & Dumontet, C. Leuk. Lymphoma 44, 1105–1111 (2003).

  8. 8

    Hunsucker, S.A., Mitchell, B.S. & Spychala, J. Pharmacol. Ther. 107, 1–30 (2005).

  9. 9

    Pieters, R. et al. Leuk. Res. 16, 873–880 (1992).

  10. 10

    Meyer, J.A. et al. Nat. Genet. 45, 290–294 (2013).

  11. 11

    Vrooman, L.M. & Silverman, L.B. Curr. Opin. Pediatr. 21, 1–8 (2009).

  12. 12

    Sharma, S.V. et al. Cell 141, 69–80 (2010).

  13. 13

    Ernst, T. et al. Leukemia 26, 1701–1703 (2012).

  14. 14

    Zhang, J. et al. Nature 481, 157–163 (2012).

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Correspondence to Jon C. Aster or Daniel J. DeAngelo.

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The authors declare no competing financial interests.

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Aster, J., DeAngelo, D. Resistance revealed in acute lymphoblastic leukemia. Nat Med 19, 264–265 (2013). https://doi.org/10.1038/nm.3119

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