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Objective To analyze the expression and clinical significance of exonucleotide pyro-phosphatase/phosphodiesterase family member 2 (ENPP2) in acute myeloid leukemia (AML), and to ex-plore its potential molecular mechanism. Methods The expression profiles of ENPP2 in different normal tissues was analyzed with GTEx database. Rstudio and Graphpad were used to analyze ENPP2 expression, genomic mutations and survival curve in data from GEO and TCGA databases, and the signaling pathway as-sociated with ENPP2 expression were further analyzed with GSEA enrichment software. Results In normal tissues, ENPP2 was mainly expressed in fat, brain and uterus;the expression in acute myeloid leukemia tis-sues was higher than that in donors. Only 0. 5％ of patients in 187 TCGA genomic data had gene amplifica-tion, there was no gene mutations and deletions. ENPP2 expression in recurrent AML was significantly high-er than primary patients, and its high expression was associated with poor prognosis. Gene enrichment anal-ysis shows high ENPP2 group isenriched in autoimmune diseases, cytokine receptor activation pathway, and low ENPP2 was enriched in DNA replication, cell cycle pathways. ENPP2 was also involved in the pathway that associated with retinoic acid and glucocorticoids treatment. Conclusions ENPP2 is highly expressed in AML patients and is associated with recurrence and poor prognosis of AML. The main molecular mecha-nism of ENPP2 in AML may be related to autoimmune response and drug treatment response, ENPP2 is a potential therapy target of AML.
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Objective@#To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants.@*Method@#The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed.@*Result@#Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients.@*Conclusion@#ENPP1 gene mutation was a cause of patient with hypophosphatemic rickets. Comorbid features included generalized arterial calcification of infancy, early onset hearing loss, pseudoxanthoma and ossification of posterior longitudinal ligament. ENPP1 gene testing should be performed on hypophosphatemic rickets patients without PHEX gene variants. Long-term follow up is recommended. The most common types of ENPP1 gene variants were nonsense/splicing variants. The gene c.783C>G was the most common variants in Chinese patients.
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Objective To study the influence of defection of Fragile X mental retardation-1 gene (FMR1) on cyclic adenosine monophosphate (cAMP) and to discuss its mechanism. Methods FMR1 gene of peripheral blood mononuclear cell was silenced in vitro by sodium nitrointroprusside. The effect of gene-silencing was detected using reverse transcript polymerase chain reaction (RT-PCR). The specific activity of adenylate cyclase and phosphodiesterase was showed by the activity ratio of yield or consumption of cAMP during a unit time. Spectrophotometry was used to measure the two key enzymes (adenylate cyclase and phosphodiesterase), as to determining the level of intracellular cyclic adenosine monophosphate in the process of cAMP metabolism. Results FMR1 gene was fully silenced by sodium nitrointroprusside at 12th, 24th and 48th hour separately, re-expressed at 72th hour. If the cultivated fluild was replaced with new sodium nitrointroprusside at 48th hour, FMR1 gene would be silenced continuously. The intracellular cAMP level in the gene silenced group was lower, and significant depression of adenylate cyclase specific activity was found in the FMR1 gene silenced group (P=0.000). No significant difference was found on phosphodiesterase specific activity (P=0.983). Conclusions The results suggest that the yield of cAMP could be influenced by defection of FMR1. The depression of adenylate cyclase activity might be one of the causes of the decrease of intracellular cAMP production.
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Objective To investigate the effect of ketamine on the phosphodiesterase (PDE) activities in lung tissue and leukocytes in rats. Methods Twenty SD rats weighing 140-160 g were randomly divided into two groups of 10 animals each : (A) ketamine group received intraperitoneal ketamine 10 mgkg-1 and (B) control group received equal volume of normal saline ip. Thirty minutes after ketamine administration the animals were sacrificed by exsanguination. Leukocytes were separated and 25 mg of lung tissue was obtained for determination of PDE activities by HPLC. Results The PDE activities in both lung tissue and leukocytes were lower in ketamine group than those in control group ( P