Expression Levels of HES1, C-MYC and NF-kB in Peripheral Blood of Patients with T Cell Acute Lymphoblastic Leukemia and Their Significance / 中国实验血液学杂志

OBJECTIVE@#To analyze and investigate the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with T cell acute lymphoblastic leukemia (T-ALL) and their significance.@*METHODS@#Sixty patients with T-ALL and 60 patients with acute myelogenous leukemia (AML) diagnosed in our hospital from June 2012 to March 2015 were enrolled in T-ALL group and AML group, respectively. Another 30 healthy people were enrolled in the control group. Peripheral blood was collected to detect the expression levels of HES1, C-MYC and NF-kB by RT-PCR. The general data and the expression of HES1, C-MYC and NF-kB in peripheral blood were compared among the patients with different type of leukemia, cytogenetical types and different prognosis.@*RESULTS@#There was no significant difference in baseline data, such as age and sex among the 3 groups (P＞0.05). The Hb level, WBC and Plt count, BM blast cell ratio in T-ALL and AML groups all were significantly higher than those in control group (P＜0.01), but there were no statistical difference in above-mentioned indicators between T-ALL and AML groups (P＞0.05). The expression levels of HES1, C-MYC and NF-kB in peripheral blood among 3 groups were significantly differenct (P＜0.01), the expressions levels of HES1, C-MYC and NF-kB in T-ALL and AML groups were significantly higher than those in control were significantly group (P＜0.01), moreover, the expression levels of above-mentional indicators in T-ALL groups were significantly higher than than those in AML group (P＜0.01). The expression levels of HES1, C-MYC and NF-kB iin T-ALL patients with poor prognosis were significantly higher than those in T-ALL patients with favorable prognosis (P＜0.01); the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with different theraptic efficacy were follow: complete remission group＜partial remission group＜no remission group (P＜0.01).@*CONCLUSION@#The HES1, C-MYC and NF-kB are highly expressed in peripheral blood of the patients with T-ALL, moreover, the expression levels maybe different, because of the cytogenetic, and theraptic efficacy.

Analysis of prognostic risk factors in childhood hemophagocytic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify and explore the prognostic risk factors of the hemophagocytic syndrome (HPS).</p><p><b>METHODS</b>A retrospective study was conducted on 50 childhood patients with HPS who were admitted to our hospital between 2007 and 2011. All their medical records were reviewed and analyzed. For each patient, demographic, laboratory data and outcome information were collected. The patients were divided into deceased or survived groups based on the follow-up results. Comparative analysis of the data was done by using independent-samples test and logistic multiple and univariate regression.</p><p><b>RESULTS</b>Among the 50 HPS patients, 30 were male and 20 female, age ranged from 3 months to 10 years. Reduction of serum albumin, cholinesterase and natural killer (NK) cells was found in the forty-six patients. The laboratory features showed an elevation of serum ferritin with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty of patients had hemophagocyte in bone marrow at diagnosis of HPS. The positive serum EBV-IgM was found in thirty-five patients.During the observation period, 25 of 37 patients (67.6%) died, while 13 of whom died within a month after hospitalization. The deceased patients were more likely to have lower albumin, cholinesterase, NK cells level and more prolonged active partial thromboplastin time than the survived patients (P < 0.05). Multivariate logistic regression analysis revealed that duration of illness > 1 month, albumin level < 25 g/L, cholinesterase level < 2000 U/L, NK cell level 0-3% and positive EBV-IgM were related with the prognosis significantly (P < 0.05 for all comparisons).</p><p><b>CONCLUSION</b>This study revealed that duration of illness > 1 month, decreases in albumin, NK cell and cholinesterase, and positive EBV-IgM were the risk factors related to mortality in children.</p>

Role of phosphatidylinositol 3-kinase and myosin light chain kinase during the activation of thrombin receptors / 中国实验血液学杂志

The objective of study was to compare the influences of wortmannin on platelet aggregation and platelet membrane surface glycoproteins GPIb expression after thrombin receptor activation, and to investigate the role of phosphatidylinositol 3-kinase (PI3-K) and myosin light chain kinase (MLCK) in the course of thrombin receptor activation. Peptide SFLLRN (PAR1-AP) and AYPGKF (PAR4-AP) were used for stimulating platelet, and the changes of platelet aggregation and GPIb were analyzed with 100 nmol/L wortmannin (inhibitor of PI3-K) and 10 micromol/L wortmannin (inhibitor of MLCK). The results indicated that the platelet activation was influenced by either concentration of wortmannin in response to PAR stimulation. Platelet aggregation was apparently inhibited by 10 micromol/L wortmannin through both PAR peptides, and was slightly inhibited by 100 nmol/L wortmannin only under PAR1-AP activation. In addition, GPIbalpha internalization was partly inhibited by 100 nmol/L wortmannin in response to PAR1 (p < 0.05 at 1, 2, 5 min) and PAR4 (p < 0.05 at 2, 5, 10 min) activation. Meanwhile, 10 micromol/L wortmannin induced little change for GPIbalpha centralisation in the course of PAR activation, with a delayed restoration of surface GPIbalpha observed under PAR1-AP activation, and no change of GPIbalpha redistribution existed under PAR4-AP activation. It is concluded that the different roles of PI3-K and MLCK exist in the course of thrombin receptor activation. PI3-K accelerates the short course of GPIb centralisation for two PAR signal pathways, while MLCK inhibits the restoration of GPIbalpha in PAR1 pathway.

Clinical significance of TNF-alpha, IL-1beta and IFN-gamma levels at early phase after allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

The objective of this study was to investigate the alterations of cytokines TNF-alpha, IL-1beta and IFN-gamma at early phase after allogeneic hematopoietic stem cell transplantation and in the course of preconditioning, and to explore the relation of these cytokines with transplant-related complications. Alterations of TNF-alpha, IL-1beta, and IFN-gamma levels in serum were detected by ELISA in 95 patients received allogeneic hematopoietic stem cell transplantation (among them 43 cases with GVHD, 5 cases with thrombosis, 31 cases with infection) and 20 in healthy adults. Alterations of the three cytokines were analyzed during the preconditioning and the early phase after transplantation. The results showed that the TNF-alpha levels in aGVHD patients underwent allo-HSCT were already higher than that in normal controls before preconditioning (p<0.01), other patients did not show significant change during this course. TNF-alpha level in all patients were higher than that at day 4 of preconditioning, then decreased at end of preconditioning (p<0.05). TNF-alpha level increased at occurrence of aGVHD, thrombosis and infection, which is most significant in patients with aGVHD, and less significant in patients with infection as compared with patients with thrombosis (p<0.05). TNF-alpha level began to increase at 2 weeks before aGVHD and thrombosis developed in patients, while TNF-alpha levels did not change in patients with infection at the same time. IL-1beta levels did not change during preconditioning, but increased at time of aGVHD, thrombosis and infection in patients, in which IL-1beta levels in patients with thrombosis increased obviously, and more obviously in patients with aGVHD than that in patients with infection (p<0.01). IL-1beta levels in patients with aGVHD began to increase at 1 week before aGHVD developed, but IL-1beta levels in patients with thrombosis began to increase at two weeks before complication developed. IFN-gamma levels did not change in all patients during the process of transplantation. It is concluded that the alterations of cytokine levels exist during the course of allo-HSCT, which reflects the vascular damage following preconditioning and occurrence of some transplant associated complications. Levels of TNF-alpha and IL-1beta are closely related to aGVHD or thrombotic complications. Monitoring changes of TNF-alpha and IL-1beta levels contributes to early discovery of aGVHD and thrombotic complications.

Clinical significance of plasminogen activator inhibitor-1 (PAI-1) in the early development of HSCT-associated thrombotic complications / 中华血液学杂志

<p><b>OBJECTIVE</b>To illustrate the early alteration of plasminogen activator inhibitor-1 (PAI-1) in the recipients of hematopoietic stem cell transplantation (HSCT) and explore its clinical significance in transplantation-associated thrombotic complications.</p><p><b>METHODS</b>Ninety-five patients undergoing HSCT were enrolled in this study. PAI-1 level and other hemostatic parameters were measured by enzyme linked immunosorbent assay (ELISA) in platelet poor plasma samples from patients on conditioning therapy and then weekly until four weeks after HSCT.</p><p><b>RESULTS</b>Significant increase in PAI-1 was detected after conditioning treatment, followed by a diminution in the very week on transplantation (week 0), then increased with in time after transplantation. According to the occurrence of transplant-associated complications, patients were classified into four groups: thrombus group \[veno-occlusive disease (VOD) (n = 5), thrombotic microangiopathy (TMA) n = 1\], aGVHD group (n = 29), infection group (n = 19) and non-complication group (n = 41). One of 30 patients (3.3%) was diagnosed as thrombus in the auto-HSCT group, while five of 65 patients (7.7%) did in the allo-HSCT group. PAI-1 level of thrombotic patients was significantly increased compared with non-thrombotic subjects, and the patients without thrombotic complications have higher PAI-1 level in the allo-HSCT group than in auto-HSCT group. All the patients with complications presented with significantly increased PAI-1 compared with those with no complications (P < 0.05). The six patients with thrombotic complications showed extremely elevated PAI-1 \[(62.8 +/- 7.5) microg/L\] compared with that of aGVHD patients \[(45.1 +/- 9.1) microg/L\] or infection patients \[(50.0 +/- 11.2) microg/L\] post-HSCT (P < 0.05).</p><p><b>CONCLUSION</b>The increase in plasma PAI-1 may be a specific mark for transplantation-associated thrombotic complications. Increased PAI-1 reflects the development of thrombotic complications. Extreme elevation of PAI-1 contributes to the early diagonsis of VOD and TMA after HSCT.</p>