Why would individuals with the lowest level of enzyme get the sickest when they take the drug?
Suggest one possible reason.
Investigating further, Dr. Ryder decides to look at drug levels in many patients who are all receiving the same standard doses of the thiopurine drug and compare them to enzyme levels. When she compares the level of thioguanine nucleotides (TGN) created by the thiopurine drug to the body’s level of TPMT enzyme in patients, this is what she finds:
Figure 4. Scatter Plot of TGN vs. Enzyme Activity Thioguanine nucleotide concentrations and TPMT enzyme activity levels in 95 Children with Acute Lymphoblastic Leukemia (ALL) who were being treated with standard doses of thiopurine drugs.
Source: Modified from Lennard L., J.S. Lilleyman, J. Van Loon, and R.M. Weinshilboum (1990) Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet 336:225–229.