ArticleHaematologica2014
Glutathione transferase-A2 S112T polymorphism predicts survival, transplant-related mortality, busulfan and bilirubin blood levels after allogeneic stem cell transplantation.
Article in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Busulfan-cyclophosphamide versus cyclophosphamide-busulfan as conditioning regimen before allogeneic hematopoietic cell transplantation: a prospective randomized trial.Annals of hematology · 2021Trial
- Glutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism.Cell death discovery · 2021Article
- Predicting the presence and mechanism of busulfan drug-drug interactions in hematopoietic stem cell transplantation using pharmacokinetic interaction network-based molecular structure similarity and network pharmacology.European journal of clinical pharmacology · 2021Article
- Total Body Irradiation Forever? Optimising Chemotherapeutic Options for Irradiation-Free Conditioning for Paediatric Acute Lymphoblastic Leukaemia.Frontiers in pediatrics · 2021Review
- Population pharmacokinetic analysis of intravenous busulfan: GSTA1 genotype is not a predictive factor of initial dose in Chinese adult patients undergoing hematopoietic stem cell transplantation.Cancer chemotherapy and pharmacology · 2020Article
- Article
- Use of Defibrotide to help prevent post-transplant endothelial injury in a genetically predisposed infant with metachromatic leukodystrophy undergoing hematopoietic stem cell gene therapy.Bone marrow transplantation · 2018Article
- GlutathioneDrug design, development and therapy · 2018Review
- Article
- Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review.Expert opinion on drug metabolism & toxicology · 2017Review
- Rare genetic variants in cellular transporters, metabolic enzymes, and nuclear receptors can be important determinants of interindividual differences in drug response.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- The Association between Gene-Environment Interactions and Diseases Involving the Human GST Superfamily with SNP Variants.International journal of environmental research and public health · 2016Review
- Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children.International journal of molecular sciences · 2015Review
- Identification and utilization of donor and recipient genetic variants to predict survival after HCT: are we ready for primetime?Current hematologic malignancy reports · 2015Review
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Busulfan liver metabolism depends on glutathione, a crucial mediator of cellular and systemic stress. Here we investigated 40 polymorphisms at 27 loci involved in hepatic glutathione homeostasis, with the aim of testing their impact on the clinical outcome of 185 busulfan-conditioned allogeneic transplants. GSTA2 S112T serine allele homozygosity is an independent prognostic factor for poorer survival (RR=2.388), for increased any time- and 100-day transplant-related mortality (RR=4.912 and RR=5.185, respectively). The genotype also predicts a wider busulfan area under the concentration-time curve (1214.36 ± 570.06 vs. 838.10 ± 282.40 mMol*min) and higher post-transplant bilirubin serum levels (3.280 ± 0.422 vs. 1.874+0.197 mg/dL). In vitro, busulfan elicits pro-inflammatory activation (increased NF-KappaB activity and interleukin-8 expression) in human hepatoma cells. At the same time, the drug down-regulates a variety of genes involved in bilirubin liver clearance: constitutive androstane receptor, multidrug resistance-associated protein, solute carrier organic anion transporters, and even GSTA2. It is worthy of note that GSTA2 also acts as an intra-hepatic bilirubin binding protein. These data underline the prognostic value of GSTA2 genetic variability in busulfan-conditioned allotransplants and suggest a patho-physiological model in which busulfan-induced inflammation leads to the impairment of post-transplant bilirubin metabolism.
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