Drug side effects explained in patients of East Asian ancestry

Jun J. Yang, PhD

The drug mercaptopurine is crucial for curing the most common childhood cancer, acute lymphoblastic leukemia (ALL). The drug is the backbone of the chemotherapy that has helped push long-term survival rates for young ALL patients to 94 percent.

But at standard doses some patients develop side effects. Patients of East Asian ancestry seem particularly prone to complications. These problems can delay treatment and jeopardize chances for cure.

St. Jude Children’s Research Hospital scientists have identified an inherited version of a gene that helps explain the added risk. They hope the discovery will lead to safer, more effective use of mercaptopurine. The gene is named NUDT15.

Researchers found that patients who inherit either one or two copies of this newly identified version of NUDT15 are extremely sensitive to mercaptopurine. At standard doses these patients develop side effects that can interrupt treatment. Patients of East Asian ancestry are more likely to carry this version of NUDT15 than are patients from other backgrounds.

The study was published online in the Journal of Clinical Oncology. Jun J. Yang, PhD, of St. Jude Pharmaceutical Sciences, is the paper’s first and corresponding author.

January 26, 2015

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