Knockout of BMAL1 Gene Induces Apoptosis of HL-60 Cells and Inhibits its Proliferation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the biological function of BMAL1 in human acute myeloid leukemia by means of the HL-60 cell line in whica circadian gene BMAL1 was konocked-out by the CRISPR/Cas9 technology.</p><p><b>METHODS</b>Two sgRNAs for BMAL1 were designed and the PX459 knockout vectors containing the sgRNA were constructed. The activity of 2 sgRNAs was detected by T7 endonuclease I. the BMAL1 knocked out HL-60 cells were prepared by transient transfection of the target vectors into the cells. Western blot was used to detect the expression of BMAL1 protein. The apoptosis of the targeted cells was detected by flow cytometry. The proliferation status of the cells was assessed by the CCK-8 assay.</p><p><b>RESULTS</b>The PX459-sgRNA vectors were successfully constructed and screened to assure the activity of the targeting vector. It was found that the expression of BMAL1 protein was not detected in BMAL1-knocked out HL- 60 cells. Further, it was shown that BMAL1 knockdout could promote the apoptosis of HL-60 cells and inhibit the cell proliferation ability.</p><p><b>CONCLUSION</b>BMAL1 knocked out HL-60 cells have bean successfully established using the CRISPR/Cas9 gene editing technique, and BMAL1 knockout can promote the HL-60 cell apoptosis and inhibit its proliferation.These result reveal the biological role of the BMAL1 circadian gene in acute myeloid leukemia.</p>

Mechanisms of sorafenib induced NB4 cell apoptosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.</p><p><b>METHODS</b>The human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.</p><p><b>RESULTS</b>As compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.</p><p><b>CONCLUSION</b>Sorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.</p>

Study on the quality of life and its related factors on patients with multiple myeloma / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the quality of life and influencing factors on patients with multiple myeloma (MM).</p><p><b>METHODS</b>227 MM cases were selected at 5 hospitals in Xi'an from August, 2010 to March, 2013. QLQ-C30 was used to evaluate the quality of life of MM patients, and their norms were as control. Factors which influencing the quality of life were investigated and analyzed with SPSS 17.0 software.</p><p><b>RESULTS</b>The total score of quality of life in MM patients was 49.0±21.7 which was lower than the norms (60.7±23.4). The scores on fatigue, nausea, vomiting, pain, short of breath, disturbance on sleeping, losing appetite, constipation, other symptoms and financial difficulty were significantly higher than data of the norms (P < 0.05). Factors as being elderly (especially those older than 70), under higher proportion of medical costs on their own expense or financial difficulty etc., had major influences on the quality of life (P < 0.05) of MM patients who in particular having worse quality of life when in worsening clinical ISS stage (P < 0.05). Low level of hemoglobin, high level of serum calcium and globulin all significantly reduced the quality of life of the MM patients (P < 0.05).</p><p><b>CONCLUSION</b>The quality of life of MM patients was significantly lower than the normal people or patients with other tumors. Fatigue, pain, and financial difficulty were main influencing factors on the quality of life of MM patients. The assessment on the effects of treatment should relate to the improvement of hemoglobin, serum calcium and globulin, which could all improve the quality of life of MM patients.</p>