NOD2 silencing promotes cell apoptosis and inhibits drug resistance in chronic lymphocytic leukemia by inhibiting the NF-κB signaling pathway.

Recent years have witnessed increasing studies on the effect of epigenetic silencing of genes in the progression of chronic lymphocytic leukemia (CLL). This study investigates whether the nucleotide binding oligomerization domain containing 2 (NOD2) participates in the cell apoptosis and drug resistance of CLL cells. Cells were treated with adriamycin (ADR), etoposide, aclacinomycin and daunorubicin. After treatment, drug resistance and cell proliferation were examined to detect the inhibitory effect of ADR on cell proliferation; flow cytometry to identify ADR accumulation, the cell cycle distribution and apoptosis after transfection, and rhodamine 123 accumulation and efflux tests to assess P-glycoprotein (P-gp) function. NOD2 silencing or inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway suppressed the multidrug resistance level in CLL, the inhibition rate, and cell proliferation caused by ADR at concentrations of approximately 0.25-1.5 µmol/L. Greater accumulation of ADR was observed in the CLL-AAT cell line than in the CLL-AAT/A02 cell line, but NOD2 silencing or inhibition of the NF-κB signaling pathway further increased the accumulation of ADR drugs in the CLL-AAT cell line and inhibited the drug efflux pump function of P-gp. Additionally, NOD2 silencing or NF-κB signaling pathway inhibition increased the apoptotic rate. The results of this study indicate that NOD2 promotes cell apoptosis and reduces the drug resistance of CLL by inhibiting the NF-κB signaling pathway.

Overexpression of long non-coding RNA HOTAIR predicts a poor prognosis in patients with acute myeloid leukemia.

The long non-coding RNA, HOX transcript antisense intergenic RNA (HOTAIR), has been indicated to have involvement in a number of cancers, however, its role in acute myeloid leukemia (AML) is unknown. The present study aimed to investigate the pattern of HOTAIR expression in AML and to evaluate its clinical significance in tumor progression. Quantitative polymerase chain reaction was performed to examine the HOTAIR expression in mononuclear cells from the bone marrow (BM) or peripheral blood specimens of 85 patients with newly diagnosed AML. The association of HOTAIR expression with the clinicopathological factors and prognosis of AML patients was statistically analyzed. The expression of HOTAIR was significantly upregulated in the AML patients compared with the healthy controls (mean expression value, 3.87±0.29 vs. 1.28±0.09; P<0.001), and markedly decreased in the patients post-treatment compared with pre-treatment (4.76±0.47 vs. 2.81±0.27; P<0.001). Moreover, high levels of HOTAIR were associated with higher white blood cell and BM blast counts (P<0.001 and P=0.001, respectively), and lower hemoglobin and platelet counts (P=0.007 and 0.001, respectively). Patients with a high level of HOTAIR expression had relatively poor overall survival (OS; 20.5 vs. 32.1 months, P=0.001) and relapse-free survival (21.5 vs. 33.6 months, P=0.001) times compared with those with a low level of HOTAIR expression. These data demonstrated that HOTAIR expression was upregulated in newly diagnosed AML patients and was associated with leukemic burden, and DFS and OS times. HOTAIR may represent a biomarker of a poor prognosis and is a potential therapeutic target for AML treatment.

Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients.

OBJECTIVE: To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen. METHODS: A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively. RESULTS: The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P > 0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P = 0.848) and progression-free survival (median 22 months versus 25 months; P = 0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%, P = 0.015). CONCLUSIONS: The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Enhancing effect of ß-elemene emulsion on chemotherapy with harringtonine, aclacinomycin, and Ara-c in treatment of refractory/relapsed acute myeloid leukemia.

Objective : This study is to determine the curative effect of ß-elemene emulsion on chemotherapy in the treatment of refractory/relapsed acute myeloid leukemia (AML). Methods : In the ß-elemene emulsion plus HAA chemotherapy (harringtonine, aclacinomycin, Ara-c group) group, 120 cases received ß-elemene emulsion (400 mg) plus the HAA treatment. A 14-day treatment was a course of treatment, followed by an 8-14 day pause, and then the next course of treatment. The HAA treatment included Ara-C, 100 mg/m2, once every 12 h from day 1 to day 7; aclacinomycin, 20 mg/m2, from day 1 to day 7; and homoharringtonine, 4 mg/m2, from day 1 to day 7. The patients in the control HAA group received HAA treatment only. For both groups, effective antibiotics were given to patients when it was necessary. Results : The total effective rate in the ß-elemene emulsion plus HAA group was 80.8%. But the total effective rate in the HAA only group was 52.9%. These results suggest that the ß-elemene emulsion plus HAA treatment has a much better curative effect in comparison with the HAA only treatment (P < 0.05). Furthermore, ß-elemene emulsion has slightly adverse response, without causing blood and bone marrow depression. Conclusion : ß-elemene emulsion has a curative effect in treatment of refractory/relapsed AML in combination with harringtonine, aclacinomycin, and Ara-c.

[Expression of DNMT gene in bone marrow of patients with acute myelogenous leukemia and its significance].

This study was aimed to explore the expression and significance of DNMT1 gene in bone marrow of patients with acute myelogenous leukemia (AML). The expression of DNMT1 gene was detected by real-time PCR in 30 healthy people and 126 AML patients. The results showed that the expression level of DNMT1 gene was lower in the 30 healthy people and was higher in AML patients. There was a marked decline in the expression level of DNMT1 gene after complete remission (CR) as compared with the initial treatment. The expression level of DNMT1 gene did not correlated with age, sex and the clinical characteristics at initial diagnosis such as white blood cell count and chromosomal karyotype in AML patients. The CR rate in AML patients with low expression level of DNMT1 gene was lower than that in those with high expression level. It is concluded that bone marrow DNMT1 gene level may play an important role in AML pathogenesis and can serve as an index in evaluating AML prognosis.