No abstract

Suppressors of cytokine signaling, SOCS1 and SOCS3, are important negative regulators of Janus kinase 2/signal transducers and activators of transcription signaling, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Curcumin has been shown to possess anticancer activity through different mechanisms. However, whether curcumin can regulate the expression of SOCS1 and SOCS3 is still unknown. Here, we found that curcumin elevated the expression of SOCS1 and SOCS3 via triggering acetylation of histone in the regions of SOCS1 and SOCS3 promoter in K562 and HEL cells. As a novel histone deacetylases (HDACs) inhibitor, curcumin inhibited HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8 but not HDAC2. Knockdown of HDAC8 by small interfering RNA markedly elevated the expression of SOCS1 and SOCS3. Moreover, ectopic expression of HDAC8 decreased the levels of SOCS1 and SOCS3. Thus, HDAC8 plays an important role in the modulation of SOCS1 and SOCS3 by curcumin. Also, trichostatin A (TSA), an inhibitor of HDACs, increased the levels of SOCS1 and SOCS3. Furthermore, curcumin increased the transcript levels of SOCS1 and SOCS3 and significantly inhibited the clonogenic activity of hematopoietic progenitors from patients with MPNs. Finally, curcumin markedly inhibited HDAC activities and decreased HDAC8 levels in primary MPN cells. Taken together, our data uncover a regulatory mechanism of SOCS1 and SOCS3 through inhibition of HDAC activity (especially HDAC8) by curcumin. Thus, being a relative non-toxic agent, curcumin may offer a therapeutic advantage in the clinical treatment for MPNs.

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been described as a possible prognostic marker in patients with acute myeloid leukemia (AML). However, the results in this field are not reproducible in different cohorts. In this study, we investigated WT1 mutations, expression levels and SNP rs16754 in a cohort of 122 adult patients with AML. As the major allele (65.6%) in a Chinese population, WT1(GG) was associated with younger age (≤ 60) and lower percentage of blasts than WT1(GA/AA). Meanwhile, improved overall survival (OS, p = 0.035) and disease-free survival (DFS, p = 0.021) were observed in WT1(GG) compared with WT1(GA/AA). We then found that WT1 mutation, occurring in 8% of patients with AML, did not predict clinical outcome. Finally, WT1 levels were higher in patients with WT1(GG) than in those with WT1(GA/AA). However, high levels of WT1 (> median) predicted worse OS (p = 0.015) and DFS (p = 0.034) than low levels of WT1 (≤ median). However, further studies are required to elucidate the mechanism of why WT1(GG), which was associated with higher median expression of WT1 that predicts worse OS and DFS compared to low expression of WT1, predicted better OS and DFS compared with WT1(GA/AA). In summary, WT1 rs16754 and WT1 expression have a significant impact on clinical outcome in patients with AML.

No abstract

Objective: To assess miR-155’s effect on aplastic anemia (AA) rats. Methods: In the present study, the healthy rats (control group) and AA rats including AA rats with miR-155 overexpression (experimental group I) and those with miR-155 deficiency (experimental group II), were selected. The levels of miR-155, STAT3 (a key gene in STAT3 signaling pathway) and phosphorylated STAT3 (p-STAT3) in control group and experimental group were detected via qPCR and Western blotting. Moreover, the number of white blood cells (WBCs), red blood cells (RBCs), platelets (PLTs) and hemoglobin (HGB) level were also measured. Results: The level of miR-155 in AA rats was significantly declined compared with that in healthy rats (p < 0.05). STAT3 mRNA level was significantly declined in AA rats with miR-155 overexpression compared with that in AA rats with miR-155 deficiency (p < 0.05). STAT3 and p-STAT3 protein expression in AA rats with miR-155 overexpression were significantly lower than those in AA rats with miR-155 deficiency (p < 0.05). Besides, it was found that the number of WBC, RBC, PLT and HGB level were significantly elevated in AA rats with miR-155 overexpression compared to those in AA rats with miR-155 deficiency (p < 0.05). Conclusion: miR-155 can improve the AA symptoms of rats through inhibiting the STAT3 signaling pathway.