Background: Pure curcumin has been reported to down-regulate the expression of WT1 in leukemic cells. However, the molecular mechanism underlying the down-regulation of WT1 by curcumin is not completely delineated. The purpose of this present study is to identify a new miRNA-mediated mechanism which plays an important role in the anti-proliferation effects of curcumin in leukemic cells. Methods: K562 and HL-60 cells were treated with different concentrations of curcumin for 24 and 48 hours, the level of miR-15a/16-1 and WT1 were detected by qRT-PCR and Western blotting. WT1 expression and cell proliferation were detected by Western blotting and CCK-8, after curcumin treated-K562 and HL-60 cells were transfected with anti-miR-15a/16-1 oligonucleotides. Results: We found that pure curcumin upregulated the expression of miR-15a/16-1 and downregulated the expression of WT1 in leukemic cells and primary acute myeloid leukemia (AML) cells. Overexpression of miR-15a/16-1 deduced the protein level of WT1 in leukemic cells, but downregulation of WT1 by siRNA-WT1 could not increase the expression of miR-15a/16-1 in leukemic cells. These results reveal that curcumin induced-upregulation of miR-15a/16-1 is an early event upstream to downregulation of WT1. Furthermore, anti-miR-15a/16-1 oligonucleotides (AMO) partly reversed the downregulation of WT1 induced by pure curcumin in leukemic cells and AMO promoted the growth of curcumin treated-K562 and HL-60 cells. Conclusion: Thus, these data suggest for the first time that pure curcumin downregulated the expression of WT1 partly by upregulating the expression of miR-15a/16-1 in leukemic cells. miR-15a/16-1 mediated WT1 downregulation plays an important role in the anti-proliferation effect of curcumin in leukemic cells.

Introduction: Peripheral monocytes have been reported to correlate with clinical outcomes in various types of malignancies. Previous reports have also shown that acute-phase thrombotic thrombocytopenic purpura (TTP) plasma could induce the activation of monocytes. However, the significance of peripheral blood absolute monocyte count (AMC) in idiopathic TTP remains an unanswered question. The primary aim of this retrospective study was to evaluate the prognostic value of AMC at admission in idiopathic TTP patients in remission.Methods: A total of 37 patients with idiopathic TTP who survived their first episode of the disease and achieved remission following treatment were eligible for inclusion in the study. SPSS and Stata were used to analysis.Results: There were 1 patient (2.7%) with low AMC (< 0.12 × 10⁹/L), 27 patients (73.0%) with normal AMC (0.12–0.80 × 10⁹/L), and 9 patients (24.3%) with high AMC (> 0.80 × 10⁹/L) at admission. Ten (27.0%) of 37 patients in our cohort subsequently relapsed (1 in the low AMC group and 9 in the normal AMC group). Survival analysis showed that there was a trend of higher relapse-free survival (RFS) rate in patients having increased A MC (log-rank test, p = 0.026). Univariate analysis revealed that increased AMC at admission was significantly associated with higher RFS (hazard ratio = 0.12, 95% confidence interval: 0.02–0.62, p = 0.011).Discussion: Our results suggest that increased AMC at admission could represent a predictor of higher RFS in TTP patients having survived their first episode of the disease and achieved remission following treatment.