Angiogenesis is important in pathophysiological processes, including the pathogenesis of acute monocytic leukemia (AML). MicroRNA‑21 (miR‑21) is overexpressed and exhibits oncogenic activity in cancer. However, the biological mechanism underlying the effect of miR‑21 in AML remains to be fully elucidated. In the present study, the expression levels of miR‑21 and vascular endothelial growth factor (VEGF) were determined in 26 patients with AML and 28 healthy individuals. The secretion of VEGF was also measured following the transfection of THP‑1 cells with miR‑21 mimic or inhibitor. The supernatants of the THP‑1 cells, which were transfected with miR‑21 mimic, inhibitor or small interfering RNA (si)VEGF, respectively, were used to incubate human umbilical vein endothelial cells (HUVECs), following which tube formation of the HUVECs was measured. miR‑21 targets were predicted using a biological target prediction website and confirmed using a luciferase assay. The effects of interleukin (IL)‑12 were investigated by examining the tube formation of HUVECs and the secretion of VEGF following recombinant human (rh) IL‑12 pretreatment. The results revealed that miR‑21 and VEGF expression was significantly increased in the peripheral blood monocytes of the patients, compared with the healthy controls. There was negative correlation between the expression of IL‑12 and miR‑21 in the serum of patients with AML. Furthermore, supernatant VEGF levels from the miR‑21 mimic‑transfected THP‑1 cells were increased, whereas a decreasing trend was observed in the miR‑21 inhibitor group. The angiogenic ability of the HUVECs pretreated with supernatant from the THP‑1 cells transfected with miR‑21 mimic was higher, and was lower in THP‑1 cells co‑transfected with miR‑21 mimic and siVEGF, compared with the miR‑21 mimic only group. A luciferase assay demonstrated that IL‑12 was the direct target of miR‑21, and the level of IL‑12 in the supernatant of THP‑1 cells transfected with miR‑21 mimic was increased. IL‑12 pretreatment increased VEGF expression and angiogenic ability in HUVECs. The inactivation of miR‑21 or activation of its target gene may be a potential therapeutic strategy in human AML.
Objective: In this study, we performed an updated meta-analysis by summarizing all available relevant association studies to evaluate whether the murine double minute-2 (MDM2) T309G polymorphism is associated with risk of leukemia and to determine its prognostic effect. Material and Methods: Studies published in PubMed, Embase and the Cochrane Controlled Trial Register were searched till June 2014 using the search terms ‘MDM2', ‘polymorphism' and ‘leukemia'. Results: Eleven studies were included in this meta-analysis, with a total of 2,478 patients accrued. There were 8 studies providing data on single nucleotide polymorphism at position 309 (SNP309) and risk of leukemia and 7 studies providing data on SNP309 and overall survival. Our analysis showed that patients having G/G mutations had a significantly higher risk of developing leukemia (HR 1.90, 95% CI 1.56-2.31, p < 0.00001), while the association between G/T and leukemia was not significant (HR 1.18, 95% CI 0.96-1.45, p = 0.11). In addition, SNP309 was not significantly associated with patient survival (HR 1.29, 95% CI 0.79-2.13, p = 0.31). Conclusions: Our meta-analysis showed that the MDM2 T309G variation, especially homozygous G/G, might be associated with an increased risk of leukemia. Additional studies are needed to confirm the findings as well as to understand the underlying mechanisms.
Objective To investigate the change and the prognostic value of platelet-associated immunoglobulin (PAIg) level in idiopathic thrombocytopenic purpura (ITP).Methods From November 2010 to October 2012,a total of 90 ITP patients in The Military General Hospital of Beijing were collected into this study,as the study group (n=90),and 40 cases with non-ITP thrombocytopenic in the same period were included in the control group (n =40).The blood specimens from the study group and the control group were collected at the clinical laboratory.The immunological phenotypes of platelet were analyzed by flow cytometry (FCM).The clinical data of the two groups were retrospectively analyzed:The expression level of PAIgG,PAIgA,and PAIgM and the platelet count were contrasted between the two groups,and the study group before and after treatment.The relationship between the changes of the PAIg level and the platelet count was analyzed.Results ①There was no significant difference in platelet count between the study group before treatment and the control group (P>0.05),but the expression level of PAIgG,PAIgA,and PAIgM was significantly higher in the study group before treatment than the control group(P<0.01).②After the treatment,the platelet count in the study group was significantly elevated than before(P<0.05),and the expression level of PAIgG,PAIgA,and PAIgM was significantly reduced than before(P<0.01).③There was a significant negative correlation between the platelet count and the expression level of PAIgG,PAIgA,PAIgM in the study group(P<0.05).Conclusions The expression level of PAIgG,PAIgA,and PAIgM can be used to evaluate the treatment efficacy and the prognosis of ITP.
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.