PRPS1 Research Articles

Research progress of PRPS1 gene and its mutations and related clinical syndrome

Phosphoribosyl pyrophosphate synthetase (PRS) 1, encoded by PRPS1 gene, is the first limiting enzyme participating in the synthetic process of nucleic acids. Consequently, it has a great effect on cell functions, especially the synthesis and metabolism of purine and pyrimidine. Some changes in PRS1 crystal structure might exert inconceivable effects on enzyme activity and lead to disorder of purine/pyrimidine metabolism, even cellular energy metabolism failure. Inherited mutation may induce disfunction of some energy-intensive tissue, the common clinical manifestations are some clinical syndrome. In addition, PRPS1 mutations found in cancer are proved to be an important cause of tumor resistance, followed by patient relapse. In a word, PRS1 plays a key role in energy metabolism, signal transduction and nucleic acid synthesis, which is of great significance in maintaining physiological activities. This article mainly focuses on the physiological functions and crystal structure of PRS1, the regulation of cell metabolism by PRPS1 gene and its mutations, as well as clinical syndromes related to PRPS1 gene mutation. Key words: Phosphoribosyl pyrophosphate; Syndrome; Metabolism; Phosphoribosyl pyrophosphate synthetase; PRPS1 gene

PRPS1 Expression in Children with Acute Leukemia and Its Clinical Significance

To investigate the correlation between the expression level of PRPS1 and the clinical characteristics in children with acute leukemia(AL). Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 mRNA and protein expression in bone marrow samples from 176 patients diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete remission), and its relevance with clinical indicators was statistically analyzed. The bone marrow samples from 21 children with non-malignant hematological disease were used as controls. (1)In B-ALL group, the level of PRPS1 mRNA in newly diagnosed patients were significantly higher than that in control and than that in complete remission patients (both P<0.0001). In T-ALL and AML group, differences was only observed between newly diagnosed patients and complete remission patients(both P<0.0001); (2)In B-ALL group, the expression level of PRPS1 increase with along risk enhancement (P<0.01), while no significant difference was observed in T-ALL (P>0.05). In AML patients, expression difference was shown between low risk group and high risk group(P<0.05); (3)High PRPS1 mRNA expression level were associated with high WBC counts and MRD positive in B-ALL patients (P=0.020, P=0.026, respectively); (4)Expression of NT5C2, an essential gene for relapse and drug resistance, was found to be positively correlated with PRPS1 expression in AL samples(P<0.05). High expression of PRPS1 is relevant factor of unfavourable prognosis in B-ALL children, which suggest PRPS1 may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.