English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Thiopurines, including azathioprine and 6-mercaptopurine (6-MP), are widely used in the treatment of autoimmune diseases and cancers, as well as prevention of rejection in organ transplantation. Azathioprine is a pro-drug that is converted to 6-MP, and subsequently undergoes extensive metabolism to the formation of 6-thioguanine nucleotides (6-TGNs). Such 6-TGNs exert their therapeutic effect by inducing apoptosis of T lymphocytes.1 Myelosuppression, manifesting as a reduction in one or more of the haematopoietic lineages (most commonly leukopenia), is a serious adverse drug reaction related to the excessive generation of 6TGNs.2 Thiopurine S-methyltransferase (TPMT) diverts 6-MP from the formation of 6-TGNs by converting 6-MP into inactive metabolites. Thus, TPMT deficiency plays a causal role in the pathogenesis of thiopurine-induced leukopenia by shunting thiopurine metabolites towards the formation of excessive 6-TGNs. Genetic variants present in the TPMT gene result in TPMT deficiency and the trait is inherited in an autosomal co-dominant manner. TPMT*1 represents the wild-type allele with normal TPMT activity while *2, *3A, *3B, *3C, and *8 account for approximately 95% of all TPMT variants known to result in TPMT deficiency.3 With the conventional dose of thiopurines, individuals who have inherited two copies of the inactive TPMT allele (homozygous deficient) experience severe myelosuppression. A significant proportion (30%60%) of individuals who have inherited one copy of the inactive TPMT allele (heterozygous deficient) develop moderate-to-severe myelosuppression. Those who carry two wild-type TPMT alleles have the least myelosuppression. Prospective TPMT genotyping has been recommended by the US Food and Drug Administration.4,5 In addition, guidelines on TPMT genotype–based dosage recommendations are currently available that include a reduced thiopurine starting dose or use of an alternative non-thiopurine treatment in individuals who carry defective TPMT allele(s).6,7 In Hong Kong, many patients are prescribed Hong Kong Med J 2016;22:185–7 DOI: 10.12809/hkmj154783

NUDT15 variant and thiopurine-induced leukopenia in Hong Kong