A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation.

The level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.

Role of caspase-10 in the death of acute leukemia cells.

Autophagy can protect cells from stress, but can also induce cancer cell death. Caspase-10 is now considered to be a factor that is associated with autophagy in cancer. The present study therefore investigated whether caspase-10 affects autophagy in acute leukemia cells. The rates of survival vs. apoptosis in acute leukemia HL-60 and Jurkat cells treated with drugs were tested using cell viability assays and flow cytometry, and the levels of caspase-3 and -10 were tested by western blotting. In HL-60 cells that were treated with chemotherapy drugs combined with a caspase-10 inhibitor, the rate of survival decreased significantly compared with HL-60 cells treated with chemotherapy drugs alone. In contrast, the rate of survival of Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor increased significantly compared with Jurkat cells treated with chemotherapy drugs alone. The results of the flow cytometry and western blotting showed that the changes in the survival rate may be caused by a change in the amount of apoptosis occurring in the Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor. However, in HL-60 cells undergoing this combination treatment, the change in the survival rate was not caused by a change in the rate of apoptosis. When HL-60 cells were treated with the chemotherapy drugs combined with the caspase-10 inhibitor and the autophagy inhibitor 3-methyl adenine, the survival rate increased, whereas the rate of apoptosis did not change. These results show that caspase-10 may be associated with autophagy in acute myeloid leukemia cells, but not in acute lymphatic leukemia cells.

RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP).

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation.

CD1d levels in peripheral blood of patients with acute myeloid leukemia and acute lymphoblastic leukemia.

The antitumor effect of natural killer T cells has been reported in several studies analyzing the expression of CD1d on antigen-presenting cells (APCs). Therefore, the present study questioned whether APCs may be abnormal in the peripheral blood (PB) of acute leukemia (AL) patients, particularly the levels of CD1d. To improve the understanding of the role of CD1d on APCs, the levels of CD1d on monocytes were analyzed in healthy controls, AL patients and AL patients with complete remission (CR). In addition, the correlation between the number of CD3+CD56+ T lymphocytes and levels of CD1d on monocytes was analyzed. Flow cytometry was used to determine the levels of CD1d on monocytes and lymphocytes. A significant decrease was observed in the levels of CD1d on monocytes in the PB of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients compared with the healthy controls. Simultaneously, significantly different levels of CD1d on monocytes were identified between the CR-AML and the CR-ALL patients; the levels of CD1d on monocytes remained low in the CR-AML patients, while the levels of CD1d on monocytes recovered in the CR-ALL patients. A significantly negative correlation was observed between the number of CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes in AL patients. However, a significantly positive correlation was identified between the cytotoxicity of the CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes. These results suggested that the significantly low levels of CD1d on monocytes may contribute to AML and ALL progression. In addition, a significant correlation was observed between the levels of CD1d on monocytes and the number/cytotoxicity of CD3+CD56+ T lymphocytes in AML and ALL patients.

Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP).

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.

[Expression of osteopontin in central nervous system leukemia and its clinical significance].

This study was aimed to investigate the expression of osteopontin (OPN) in central nervous system leukemia (CNSL) and to understand its clinical significance. The expression level of OPN in serum of 62 pediatric patients (22 cases of CNSL, 20 cases of acute leukemia without extramedullary infiltration and 20 cases of nontumor patients) and 19 cases of CNSL with complete remission (CR)were assayed by ELISA; the expression changes of OPN mRNA in bone marrow of the CNSL patients were detected by RT-PCR. The results indicated that the serum OPN level was significantly higher in CNSL group (25.21 ± 6.87 ng/ml) than that in acute leukemia group (13.24 ± 2.73 ng/ml) (P < 0.001) and nontumorous group (3.14 ± 1.60 ng/ml) (P < 0.001); the serum OPN level (4.35 ± 1.50 ng/ml) in CNSL group with CR decreased obviously (P < 0.001) after therapy; RT-PCR analysis showed that the expression of OPN mRNA was higher in CNSL group as compared with other two groups (P < 0.01). It is concluded that the OPN expression may play a role in central nervous system infiltration of leukemia, the mechanism of which remains to need further clinical exploration.