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To investigate the expression level and analyze the clinical significance of NT5C2, which is an nucleoside analogues metabolism related gene, in children with acute leukemia (AL).Real-time PCR and immunohistochemistry were presented to detect the level of NT5C2 mRNA and its protein product cN- Ⅱ in bone marrow samples of 63 patients initially diagnosed with AL, 15 patients who achieved complete remission, 7 patients who relapsed and 16 non- hematologic malignancie controls. The expression of NT5C2 mRNA in different groups of AL and its relevance with clinical indicators were analyzed.①The expression of NT5C2 mRNA in newly diagnosed B-ALL, TALL, AML and controls were 1.16 (0.89-2.25, 0.96 (0.74-1.25, 1.66 (0.84-3.15) and 0.88 (0.61-1.21), respectively. NT5C2 mRNA expression in AML (P0.01) and B-ALL (P0.05) cases were higher than that in controls; NT5C2 mRNA expression in T- ALL and in controls showed no significant difference (P0.05). Changes of NT5C2 mRNA level were observed between preliminary diagnosis and complete remission in 15 patients. NT5C2 mRNA levels were significantly decreased in complete remission stage than that in newly diagnosis AL (P0.01). NT5C2 mRNA levels of relapsed-refractory group were higher than that of complete remission group and controls (P0.01). ② Immunohistochemical staining results revealed that NT5C2 protein levels were consistent with the trend of mRNA levels. ③NT5C2 mRNA levels in AML (r=0.434) and T-ALL (r=0.389) were positively correlated with risk classification (P0.05). ④ During chemotherapy of patients with AML, the NR rate of bone marrow in NT5C2 high expression group was higher than that of low expression group after 9 days induction chemotherapy (35.2% vs 0) and before consolidation therapy (25.0% vs 0); The positive rate of minimal-residual disease (36.4% vs 14.3%) and relapse rate of AL (38.5% vs 28.6%) were increased in NT5C2 high expressed patients than that in low expressed patients, but all the differences were insignificant (P0.05).High expression of NT5C2 was found to be a related risk factor of AL children with unfavourable prognosis. NT5C2 promises a new target for guiding individualized chemotherapy and evaluating the prognosis of childhood acute leukemia and monitoring recurrence.

To establish a hemophagocytic lymphohistiocytosis (HLH)-like mouse model induced by CpG oligodeoxynucleotide (CpG-ODN1826) and interferon (IFN)-γ for further study on therapy.Wild type adult C57BL/6 mice were administered with PBS or CpG-ODN1826 (50 μg) by intraperitoneal injection every two day and IFN-γ subcutaneous injection every day. Parameters of HLH were evaluated on day 10.As compared to control, HLH-like symptoms in CpG group were characterized with pancytopenia accompanied by increased ratios of monocytes, alanine aminotransferase [(198.7±54.2)IU/L], triglyceride level [(12.1±0.6)g/L], and serum ferritin [(708.4±11.8)pmol/L]; decreased albumin [(217.7±4.3)g/L], fibrinogen [(17.1±1.9)g/L] (all P0.05). Hepatosplenomegaly was obvious in CpG group. The liver in CpG group had multifocal hepatocytes necrosis and perivascular inflammations. Spleen had expanding red pulp and hyperplastic nucleated cells. Furthermore, macrophages in the liver and spleen were largely activated. Hemophagocytosis were observed in liver, spleen and bone marrow smear. The CpG group was alive during experiment, other than significant decreased activity after the first injection of CpG-ODN.These data demonstrate that repeated administration of CpG-ODN1826 and IFN-γ could induce HLH-like symptoms without fatal condition in wild type C57B/L mice. This protocol could establish a mild HLH-like mouse model, which could be useful for further study on HLH.