Systematic review and meta-analysis: transplanted hematopoietic stem cells and killer cells on leukemia.

BACKGROUND: meta-analysis was performed to study the therapeutic effect of hematopoietic stem cell transplantation combined with killer cells (important immune cells of the body) on leukemia, hoping to enhance the postoperative therapeutic efficiency. METHODS: literatures were searched with "Hematopoietic stem cell transplantation", "killer cell", "leukemia", "Cytokine induction", etc. as search terms using Boolean logic search. Review Manager was utilized for meta-analysis after literature screening. RESULTS: eleven literatures were included, most of which were of low-risk bias (medium-high quality). Through meta-analysis, statistical heterogeneity was found in non-recurring mortality (NRM) between control group and experimental group (Chi2 =15.69, I2=62%, P=0.02). The leukemia-free survival rate between two groups was not heterogeneous (Chi2 =13.16, I2=32%, P=0.16), without considerable difference between groups (Z=1.52, P=0.13). The incidence of graft-versus-host disease (GvHD) between the two groups was statistically heterogeneous (Chi2 =21.38, I2=67%, P=0.003). The incidence of graft-versus-host disease in experimental group was greatly inferior to controls (Z=3.87, P=0.0001). DISCUSSION: hematopoietic stem cell transplantation combined with killer cells can effectively reduce the incidence of GvHD after stem cell transplantation in patients. The prognosis of transplantation was good, and it had no obvious effect on the overall survival rate and recurrence rate.

[Knockout of BMAL1 Gene Induces Apoptosis of HL-60 Cells and Inhibits its Proliferation].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Downregulation of microRNA­21 expression inhibits proliferation, and induces G1 arrest and apoptosis via the PTEN/AKT pathway in SKM­1 cells.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and may progress to acute myeloid leukemia (AML). MicroRNAs (miRNA/miRs) as oncogenes or tumor suppressors regulate a number of biological processes including cell proliferation, cell cycle and apoptosis in different types of cancer cells. Recently, it has been reported that miR­21 as an oncogene is overexpressed and directly targets SMAD­7 in MDS. However, little is known about the mechanism of miR­21 in the progression of MDS. In the present study, the role of miR­21 in the proliferation and apoptosis of SKM­1 cells, an acute myeloid leukemia cell line established in the AML/MDS leukemic phase was investigated. The present results demonstrated that downregulation of miR­21 inhibited proliferation, induced apoptosis and caused G1 phase cell cycle arrest of SKM­1 cells. In addition, the expression levels of apoptosis regulator Bcl­2 (bcl2), cyclinD1 and phosphorylated­protein kinase B (AKT) were significantly decreased in SKM­1 cells transfected with the miR­21 inhibitor, whilst the expression levels of phosphatase and tensin homolog (PTEN), bcl­associated protein X (bax) and cleaved caspase 3 were significantly elevated. Furthermore, knockdown of Akt by small interfering (si)RNA significantly increased the expression of bax, cleaved caspase 3 and reduced the expression of bcl2 and cyclinD1 in SKM­1 cells. Taken together, these data indicate that miR­21 targets the PTEN/AKT pathway in the pathogenesis of MDS and could be a potential target for MDS therapy.

Sorafenib inhibited cell growth through the MEK/ERK signaling pathway in acute promyelocytic leukemia cells.

The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respectively. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analysis were performed to assess the expression of caspase-3, caspase-8, myeloid cell leukemia (MCL)1, cyclin D1, mitogen-activated protein kinase (MEK), phosphorylated (P)-MEK, extracellular signal-regulated kinase (ERK) and P-ERK. The results of the MTT assay demonstrated that, compared with untreated cells, the proliferation of sorafenib-treated NB4 cells was inhibited dose- and time-dependently. Furthermore, cell cycle arrest was induced in the G0/G1 phase and cell apoptosis was promoted in a dose-dependent manner in sorafenib-treated NB4 cells compared with untreated cells. In addition, the expression of the proapoptotic molecules caspase-3 and caspase-8 was significantly upregulated, and the expression of the antiapoptotic molecule MCL1 and the cell cycle-associated cyclin D1 was downregulated in sorafenib-treated NB4 cells compared with untreated cells. Furthermore, the phosphorylation of MEK and ERK was inhibited in sorafenib-treated NB4 cells compared with untreated cells. Sorafenib may inhibit proliferation and induce cell cycle arrest and apoptosis in APL cells. The underlying mechanisms of such effects may be associated with alterations to the expression of apoptosis-associated and cell cycle-associated molecules via MEK/ERK signaling pathway inhibition.

[Mechanisms of sorafenib induced NB4 cell apoptosis].

OBJECTIVE: To investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Study on the quality of life and its related factors on patients with multiple myeloma].

OBJECTIVE: To evaluate the quality of life and influencing factors on patients with multiple myeloma (MM). METHODS: 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. RESULTS: 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). CONCLUSION: 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.