Gene Approach

2.1.1. 6-Mercaptopurine and TPMT

The thiopurine S-methyltransferase (TPMT) genetic polymorphism has long served as a prototype of the clinical potential of pharmacogenetics. TPMT is a cytosolic metabolizing enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), 6-thioguanine, and azathioprine. In patients with exceptionally low TPMT activity (~1 in 300 individuals), thiopurine drugs may cause severe and sometimes life-threatening hematopoietic toxicity (9,10,11,12,13). Therefore, substantial (~ 10-fold) dosage reduction is required in patients with the homozygous mutant TPMT genotypes to avoid toxicity (13,14,15).

In Caucasians, the three most common variant genotypes, TPMT*3A (Ala154Thr and Tyr240Cys), TPMT*3C (Tyr240Cys), and TPMT*2 (Ala80Pro), account for >95% of the low-activity phenotypes. The U.S. FDA has added TPMT genetic information to the package inserts of thiopurine drugs, which recommends TPMT testing (genotypic testing for TPMT*3A, *3C, and *2 and/or phenotypic testing of thiopurine nucleotides and TPMT activity in erythrocytes) if patients exhibit clinical or laboratory evidence of severe toxicity, particularly myelosuppression.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment