Background: Encephalopathy is a rare drug toxicity of fluorouracil therapy. Toxicity from fluorouracil therapy is known to be associated with the individual genetic background of the enzymes, thymidylate synthase and dihydropyrimidine dehydrogenase. Methods: Two patients with advanced gastric cancer and metastatic pancreatic cancer who received 5-fluorouracil-based chemotherapy presented with acute mental change and hyperammonemia. To evaluate the genetic background of the fluorouracil-associated hyperammonemic encephalopathy, analysis of the polymorphisms of the TYMS, DPYD and MTHFR genes was performed. Results: The patients revealed to be TYMS suppressors showing homogenous deletion of 6 bp in the 3′-UTR and 3RC/3RC genotype in the promoter enhancer region (TSER), respectively. Conclusion: Genetic polymorphisms of the TYMS gene would contribute to the 5-fluorouracil-associated hyperammonemic encephalopathy. The prospective validation of the clinical implication of TYMS gene polymorphisms is warranted.

Park CH, et al. J Korean Med Sci. 2010 Dec;25(12):1818-1820. http://dx.doi.org/10.3346/jkms.2010.25.12.1818

Shin SY, et al. Blood Res. 2016 Sep;51(3):181-186. https://doi.org/10.5045/br.2016.51.3.181

Acute myeloid leukemia (AML) patients are at risk of bleeding due to disease-related lack of platelets and systemic coagulopathy. Platelets play a role in hemostasis. Leukemic blasts have been shown to alter platelet activation in vitro. Here we investigated biomarkers associated with thrombocytopenia in normal karyotype AML (NK-AML). From The Cancer Genome Atlas database, case-control study was performed between normal karyotype (NK) platelet-decreased AML (PD-AML, platelet count < 100 × 10⁹/L, n = 24) and NK platelet-not-decreased AML (PND-AML, with platelet count ≥ 100 × 10⁹/L, n = 13). Differentially expressed gene analysis, pathway analysis and modelling for predicting platelet decrease in AML were performed. DEG analysis and pathway analysis revealed 157 genes and eight pathways specific for PD-AML, respectively. Most of the eight pathways were significantly involved in G-protein-coupled receptor-related pathway, cytokine-related pathway, and bone remodeling pathway. Among the key genes involved in at least one pathway, three genes including CSF1R, TNFSF15 and CLEC10A were selected as promising biomarkers for predicting PD-AML (0.847 of AUC in support vector machine model). This is the first study that identified biomarkers using RNA expression data analysis and could help understand the pathophysiology in AML with low platelet count.

Huh HJ, et al. Ann Lab Med. 2017 Jan;37(1):81-83. https://doi.org/10.3343/alm.2017.37.1.81

Chang-Hun Park, M.D., Kiyoung Yoo, M.D., Ki-O Lee, M.T., Sun-Hee Kim, Ph.D., Ki-Woong Sung, Ph.D., and Hee-Jin Kim, Ph.D.. Ann Lab Med 2016;36:182-4. https://doi.org/10.3343/alm.2016.36.2.182