Research progress of NT5C2 in disease and treatment

doi:10.16352/j.issn.1001-6325.2023.05.0852

Abstract

Abstract: Cytosolic 5'-nucleotidase Ⅱ(cN-Ⅱ), the protein encoded by NT5C2, can catalyze the dephosphory-lation of nucleoside monophosphate and is mainly involved in the regulation of purine nucleotide pool in cells. High expression of cN-Ⅱ mRNA is associated with poor prognosis of patients with acute leukemia (AL). Acquired NT5C2 mutation will hinder the formation of DNA and thioguanine nucleotide (TGN) conjugate, resulting in 6-mercaptpurine(6-MP) resistance. In addition, NT5C2 is a risk factor associated with type Ⅱ diabetes, schizophrenia and other diseases.

Key words: NT5C2, cytosolic 5'-nucleotidase Ⅱ(cN-Ⅱ), nucleoside analogue, acute leukemia(AL), type 2 diabetes

CLC Number:

Q915

SHU Ling, HUO Bennian, SONG Lin. Research progress of NT5C2 in disease and treatment[J]. Basic & Clinical Medicine, 2023, 43(5): 852-856.

References

[1]Pesi R, Allegrini S, Balestri F, et al. Cytosolic 5'-nucleotidase Ⅱ is a sensor of energy charge and oxidative stress: a possible function as metabolic regulator[J].Cells, 2021,10:182.doi: 10.3390/cells10010182
[2]Goncharova IA, Bragina EY, Zhalsanova IZ, et al. Putative regulatory functions of SNPs associated with bronchial asthma, arterial hypertension and their comorbid phenotype[J]. Vavilovskii Zhurnal Genet Selektsii, 2021,25:855-863.
[3]Jiang C, Yang W, Moriyama T, et al. Effects of NT5C2 germline variants on 6-mecaptopurine metabolism in children with acute lymphoblastic leukemia[J].Clin Pharmacol Ther, 2021,109:1538-1545.
[4]Duarte RRR, Bachtel ND, Côtel MC, et al. The psychiatric risk gene NT5C2 regulates adenosine monophosphate-activated protein kinase signaling and protein translation in human neural progenitor cells[J].Biol Psychiatry, 2019,86:120-130.
[5]Moriyama T, Liu S, Li J, et al. Mechanisms of NT5C2-mediated thiopurine resistance in acute lymphoblastic leukemia[J].Mol Cancer Ther, 2019,18:1887-1895.
[6]Johanns M, Kviklyte S, Chuang SJ, et al. Genetic deletion of soluble 5'-nucleotidase Ⅱ reduces body weight gain and insulin resistance induced by a high-fat diet[J].Mol Genet Metab, 2019,126:377-387.
[7]Liu H, Sun Y, Zhang X, et al. Integrated analysis of summary statistics to identify pleiotropic genes and pathways for the comorbidity of schizophrenia and cardiometabolic disease[J]. Front Psychiatry, 2020,11:256.doi: 10.3389/fpsyt.2020.00256.
[8]Saliba J, Evensen NA, Meyer JA, et al. Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia[J].Pediatr Blood Cancer, 2020,67:e28306. doi: 10.1002/pbc.28306
[9]Hunsucker SA, Mitchell BS, Spychala J. The 5'-nucleotidases as regulators of nucleotide and drug metabolism[J].Pharmacol Ther, 2005,107:1-30.
[10]Walldén K, Stenmark P, Nyman T, et al. Crystal structure of human cytosolic 5'-nucleotidase Ⅱ: insights into allosteric regulation and substrate recognition[J].J Biol Chem, 2007,282:17828-17836.
[11]Mazzon C, Rampazzo C, Scaini MC, et al. Cytosolic and mitochon-drial deoxyribonucleotidases: activity with substrate analogs, inhibitors and implications for therapy[J].Biochem Pharmacol, 2003,66:471-479.
[12]Jeha S, Pei D, Choi J,et al.Improved CNS control of childhood acute lymphoblastic leukemia without cranial irradiation: St Jude Total Therapy Study 16[J]. J Clin Oncol, 2019,37:3377-3391.
[13]Hunger SP, Raetz EA. How I treat relapsed acute lymphoblastic leukemia in the pediatric population[J].Blood, 2020,136:1803-1812.
[14]Barz MJ, Hof J, Groeneveld-Krentz S, et al. Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia[J].Blood, 2020,135:921-933.
[15]王艳珍,安曦洲,刘江华,等.NT5C2基因在儿童急性白血病中的表达及其临床意义[J].中华血液学杂志,2015,9:748-753.
[16]吴遐,郝磊,薛冰,等.NT5C2在急性淋巴细胞白血病中表达水平的观察[J].中华检验医学杂志,2016,39:501-505.
[17]Antić Ž, Yu J, Van Reijmersdal SV, et al. Multiclonal complexity of pediatric acute lymphoblastic leukemia and the prognostic relevance of subclonal mutations[J].Haematologica, 2021,106:3046-3055.
[18]周海,吴晓玲,林明欣,等.基于网络药理学探讨加味桃核承气汤防治糖尿病肾病的作用机制[J].中国实验方剂学杂志,2019,25:176-186.
[19]Singgih EL, van der Voet M, Schimmel-Naber M, et al. Investigating cytosolic 5'-nucleotidase Ⅱ family genes as candidates for neuropsychiatric disorders in drosophila (114/150 chr)[J].Transl Psychiatry, 2021,11:55.doi: 10.1038/s41398-020-01149-x.
[20]Xie X, Liu F, Xue Q, et al. Association between NT5C2 rs11191580 and autism spectrum disorder in the Chinese Han population[J].Asian J Psychiatr, 2020,53:102231.doi: 10.1016/j.ajp.2020.102231.
[21]Xie X, Liu F, Xue Q, et al. Association between NT5C2 rs11191580 and autism spectrum disorder in the Chinese Han population[J].Asian J Psychiatr, 2020,53:102231.doi: 10.1016/j.ajp.2020.102231.
[22]Wang Z, Zhang J, Lu T, et al. Replication of previous GWAS hits suggests the association between rs4307059 near MSNP1AS and autism in a Chinese Han population[J].Prog Neuropsychopharmacol Biol Psychiatry, 2019,92:194-198.
[23]Naseer MI, Abdulkareem AA, Pushparaj PN, et al. Exome analysis identified novel homozygous splice site donor alteration in nt5c2 gene in a saudi family associated with spastic diplegia cerebral palsy, developmental delay, and intellectual disability[J]. Front Genet, 2020,11:14.doi: 10.3389/fgene.2020.00014.
[24]Chen X, Zhang Z, Wang X, et al. NT5C2 gene polymorphisms and the risk of coronary heart disease[J]. Public Health Genomics, 2020,23:90-99.
[25]Vishnolia KK, Hoene C, Tarhbalouti K, et al. Studies in zebrafish demonstrate that CNNM2 and NT5C2 are most likely the causal genes at the blood pressure-associated locus on human chromosome 10q24.32[J]. Front Cardiovasc Med, 2020,7:135. doi: 10.3389/fcvm.2020.00135.
[26]Dieck CL, Ferrando A. Genetics and mechanisms of NT5C2-driven chemotherapy resistance in relapsed ALL[J].Blood,2019,133:2263-2268.