scholarly journals Multilocus Genotypes of Relevance for Drug Metabolizing Enzymes and Therapy with Thiopurines in Patients with Acute Lymphoblastic Leukemia

2013 ◽  
Vol 3 ◽  
Author(s):  
Gabriele Stocco ◽  
Raffaella Franca ◽  
Federico Verzegnassi ◽  
Margherita Londero ◽  
Marco Rabusin ◽  
...  
Author(s):  
Kanyarat Khaeso ◽  
Nontaya Nakkam ◽  
Patcharee Komwilaisak ◽  
Piyathida Wongmast ◽  
Su-on Chainansamit ◽  
...  

AbstractGenetic polymorphisms of thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes have been proposed as key determinants of 6-mercaptopurine (6-MP)-induced myelosuppression in pediatric acute lymphoblastic leukemia (ALL). In the present study, genotypes of TPMT and NUDT15 were investigated in 178 Thai pediatric patients with ALL by the TaqMan SNP genotyping assay and DNA sequencing. The frequency of TPMT*3C was 0.034. Among NUDT15 variants, NUDT15*3 is the most common variant with the allele frequency of 0.073, whereas those of NUDT15*2, NUDT15*5, and NUDT15*6 variants were 0.022, 0.011, and 0.039. These data suggest that a high proportion of Thai pediatric ALL patients may be at risk of thiopurine-induced myelosuppression.


2021 ◽  
Vol 11 (8) ◽  
pp. 783
Author(s):  
Thawinee Jantararoungtong ◽  
Supaporn Wiwattanakul ◽  
Rawiporn Tiyasirichokchai ◽  
Santirhat Prommas ◽  
Rattanaporn Sukprasong ◽  
...  

The response to 6-mercaptopurine (6-MP) can be altered by genetic polymorphisms in genes encoding drug-metabolizing enzymes and drug transporters. The purpose of this study was to investigate the association between genetic polymorphisms of drug-metabolizing enzymes (TPMT 719A > G (*3C), ITPA 94C > A and ITPA 123G > A) and drug transporters (MRP4 912C > A and MRP4 2269G > A) with 6-MP-related myelotoxicity and hepatotoxicity in Thai children with acute lymphoblastic leukemia (ALL). The prescribed dosage of 6-MP and its adverse effects were assessed from medical records during the first 8 weeks and 9–24 weeks of maintenance therapy. Children with the TPMT*1/*3C genotype had a higher risk of leukopenia with an odds ratio (OR) of 4.10 (95% confidence interval (CI) of 1.06–15.94; p = 0.033) compared to wild type (TPMT*1/*1) patients. Heterozygous TPMT*3C was significantly associated with severe neutropenia with an increased risk (OR, 4.17; 95% CI, 1.25–13.90); p = 0.014) during the first 8 weeks. No association was found among ITPA94C > A, ITPA123G > A, MRP4 912C > A, and MRP4 2269G > A with myelotoxicity and hepatotoxicity. The evidence that TPMT heterozygotes confer risks of 6-MP-induced myelotoxicity also supports the convincing need to genotype this pharmacogenetic marker before the initiation of 6-MP therapy.


2005 ◽  
Vol 79 (3) ◽  
pp. 202-205 ◽  
Author(s):  
S. Pakakasama ◽  
E. Mukda ◽  
W. Sasanakul ◽  
P. Kadegasem ◽  
U. Udomsubpayakul ◽  
...  

2009 ◽  
Vol 33 (7) ◽  
pp. 898-901 ◽  
Author(s):  
Vanessa da Silva Silveira ◽  
Renata Canalle ◽  
Carlos Alberto Scrideli ◽  
Rosane Gomes de Paula Queiroz ◽  
Heloisa Bettiol ◽  
...  

2010 ◽  
Vol 3 (3) ◽  
pp. 103-108 ◽  
Author(s):  
Chumphorn Banklaui ◽  
Sumalee Jindadamrongwech ◽  
Ruchchadol Sawangpanich ◽  
Suntaree Apibal ◽  
Suradej Hongeng ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document