WHAT IS KNOWN AND OBJECTIVE: Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP. METHODS: Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated. RESULTS AND DISCUSSION: Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected. WHAT IS NEW AND CONCLUSION: Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.
WHAT IS KNOWN AND OBJECTIVE: Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP. METHODS:Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated. RESULTS AND DISCUSSION: Acute lymphoblastic leukaemiapatients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected. WHAT IS NEW AND CONCLUSION: Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.
Authors: Nicholas C K Valerie; Anna Hagenkort; Brent D G Page; Geoffrey Masuyer; Daniel Rehling; Megan Carter; Luka Bevc; Patrick Herr; Evert Homan; Nina G Sheppard; Pål Stenmark; Ann-Sofie Jemth; Thomas Helleday Journal: Cancer Res Date: 2016-08-16 Impact factor: 12.701
Authors: R Franca; P Rebora; N Bertorello; F Fagioli; V Conter; A Biondi; A Colombini; C Micalizzi; M Zecca; R Parasole; F Petruzziello; G Basso; M C Putti; F Locatelli; P d'Adamo; M G Valsecchi; G Decorti; M Rabusin Journal: Pharmacogenomics J Date: 2015-12-08 Impact factor: 3.550