Differential effects of thiopurine methyltransferase (TPMT) and multidrug resistance-associated protein gene 4 (MRP4) on mercaptopurine toxicity.

ABSTRACT:

Purpose

Mercaptopurine plays a pivotal role in treatment of acute lymphoblastic leukemia (ALL) and autoimmune diseases, and inter-individual variability in mercaptopurine tolerance can influence treatment outcome. Thiopurine methyltransferase (TPMT) and multi-drug resistant Protein 4 (MRP4) have both been associated with mercaptopurine toxicity in clinical studies, but their relative contributions remain unclear.

Methods

We studied the metabolism of and tolerance to mercaptopurine in murine knockout models of Tpmt, Mrp4, and both genes simultaneously.

Results

Upon mercaptopurine treatment, Tpmt ^-/- Mrp4 ^-/- mice had the highest concentration of bone marrow thioguanine nucleotides (8.5 pmol/5 × 10⁶ cells, P = 7.8 × 10^-4 compa

SUBMITTER: Liu C 

PROVIDER: S-EPMC5628515 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature