Research Progress on Artemisinin and Its Derivatives against Hematological Malignancies / 中国结合医学杂志

Although current therapeutic methods against hematological malignancies are effective in the early stage, they usually lose their effectiveness because of the development of drug resistances. Seeking new drugs with significant therapeutic effects is one of the current research hotspots. Artemisinin, an extract from the plant Artemisia annua Linne, and its derivatives have excellent antimalarial effects in clinical applications as well as excellent safety. Recent studies have documented that artemisinin and its derivatives (ARTs) also have significant effects against multiple types of tumours, including hematological malignancies. This review focuses on the latest research achievements of ARTs in the treatment of hematological malignancies as well as its mechanisms and future applications. The mechanisms of ARTs against different types of hematological malignancies mainly include cell cycle arrest, induction autophagy and apoptosis, inhibition of angiogenesis, production of reactive oxygen species, and induction of differentiation. Additionally, the review also summarizes the anticancer effects of ARTs in many drug-resistant hematological malignancies and its synergistic effects with other drugs.

JAK2V617F mutation and TNF-α expression in myeloproliferative neoplasms and their correlation / 中国实验血液学杂志

This study was aimed to explore the JAK2V617F mutation and TNF-α expression in patients with myeloproliferative neoplasm (MPN), and the relation between them so as to provide theoretical basis for clinical practice and target therapy. Sixty-two confirmed BCR-ABL-negative MPN patients and 15 healthy adults were enrolled in this study. The peripheral blood mononuclear cells of the patients and healthy controls were divided into two parts, one part was used to extract DNA, the other one was used to extract mRNA and reverse-transcribe into cDNA. Real-time fluorescent quantitative PCR was used to detect JAK2V617F mutation proportion and the expression level of TNF-α. The results showed that the positive rate of JAK2V617F mutation in MPN patients was 64.52% (40/62) , including 54.28% in essential thrombocythemia (ET) patients (19/35), 94.74% in polycythemia vera (PV) patients (18/19) and 37.50% in myelofibrosis (MF) (3/8) patients. Mutation proportions of JAK2V617F in ET, PV and MF patients were 0.838 ± 0.419, 4.417 ± 0.658, 2.746 ± 2.009 respectively. The expression of TNF-α in ET, PV and MF patients were higher than that in healthy controls: 1.7, 7.0, 8.2-fold (P < 0.05) respectively. In addition, TNF-α expression was correlated with JAK2V617F allele burden (Pearson r = 0.610,R(2) = 0.372,P = 0.005). It is concluded that TNF-α plays an important role in the pathogenesis of MPN, the TNF-α expression increases and is different in ET,PV and MF patients,which correlates with JAK2V617F allele burden.

Expression of TIM-1 and TIM-3 in spleen mononuclear cells and their role in Th1 polarization in primary immune thrombocytopenia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of T cell immunoglobulin mucin (TIM)-1, TIM-3 and T cell-specific transcription factors T-bet and GATA-3 in spleen mononuclear cells in patients with primary immune thrombocytopenia (ITP).</p><p><b>METHODS</b>The spleen samples were obtained from 17 active ITP patients and 10 controls with spleen traumatic rupture. By using real-time quantitative polymerase chain reaction, the mRNA expressions of TIM-3, TIM1, T-bet and GATA-3 were studied in all subjects.</p><p><b>RESULTS</b>TIM-3 mRNA levels of active ITP patients were significantly decreased to (29 ± 16)% of that of control, TIM-1 mRNA levels of active ITP patients increased to (3.20 ± 2.18) folds of that of control, but the difference was not significant. The ratio of TIM-1/ TIM-3 was elevated in active ITP patients. T-bet mRNA levels were up-regulated in ITP patients by (2.82 ± 1.57) folds (P<0.05) and the expression of GATA3 was decreased by 14% folds (P<0.05) compared to controls. The ratio of T-bet/GATA3 were significantly elevated in ITP patients.</p><p><b>CONCLUSION</b>The imbalance between TIM-3 and TIM-1 expression might play an important role in pathogenesis of ITP.</p>

JAK2V617F mutation and p-STAT5 protein expression in peripheral blood cells of patients with myeloproliferative neoplasm and their relations with clinical features / 中国实验血液学杂志

This study was aimed to explore the JAK2V617F mutation and p-STAT5 expression in patients with myeloproliferative neoplasm (MPN), and investigate their relations with clinical characteristics so as to provide theoretical basis for clinical practice and target therapy. Forty-five confirmed BCR-ABL-negative MPN patients and 15 healthy adults were enrolled in this study. Real-time fluorescent quantitative PCR and Western blot were respectively used to detect JAK2V617F mutation proportion and p-STAT5 expression level. In addition, their relations with clinical characteristics of MPN were analyzed. The results showed that the positive rate of JAK2V617F mutation in MPN patients was 73.3% (33/45), including 83.3% in polycythemia vera (PV) patients (20/24), 68.8% in essential thrombocythemia (ET) patients (11/16) and 40.0% in idiopathic myelofibrosis (IMF) patients (2/5). Mutation proportions of JAK2V617F in PV, ET and IMF patients were 0.472 ± 0.245, 0.216 ± 0.162, 0.435 ± 0.239 respectively; gray values of p-STAT5 protein in PV, ET and IMF patients were 1.396 ± 0.758, 0.760 ± 0.623, 0.792 ± 0.612 respectively. JAK2V617F mutation proportion and p-STAT5 protein expression level showed a linear correlation (P < 0.05). PV patients with higher JAK2V617F mutation proportion had higher white blood cell count, hemoglobin level and hematocrit, but lower platelet count; ET patients with higher mutation proportion showed older and higher white blood cell count, hemoglobin level and hematocrit, there was no significant difference between platelet count; IMF patients with higher JAK2V617F mutation proportion showed lower white blood cell count, platelet count, hemoglobin level and hematocrit. Patients with JAK2V617F positive mutation were more likely complicated by splenomegaly, bleeding and thrombotic events. It is concluded that the incidence rate of JAK2V617F mutation is high in patients with MPN. Higher mutation proportion always connected with higher expression of p-STAT5, and easily complicates by splenomegaly and thrombotic events.

The study of IL-18 and IL-18BP balance in aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of IL-18 and IL-18BP balance in aplastic anemia (AA).</p><p><b>METHODS</b>A total of 29 AA patients and 22 controls were recruited in present research. The expressions of IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of IL-18 and IL-18BP were measured in all subjects using real-time quantitative polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The levels of the IL-18 in plasma of AA and normals were (365.5 ± 160.6) pg/ml and (175.9 ± 92.8) pg/ml (P < 0.01); and the expression of IL-18 in severe AA patients (441.3 ± 116.9) pg/ml were higher than that in non-severe AA patients (326.4 ± 167.0) pg/ml (P < 0.05). The level of IL-18BP was increased in plasma of AA (1788.6 ± 523.8) pg/ml than in normals (1083.6 ± 489.6) pg/ml (P < 0.05). But the ratio of IL-18/IL-18BP in AA patients was much higher than that in controls (P < 0.05). RT-PCR revealed the levels of IL-18 and IL-18BP mRNA were up-regulated in AA patients when compared to controls, but the ratio of IL-18/IL-18BP was significantly elevated in AA patients.</p><p><b>CONCLUSION</b>IL-18/IL-18BP imbalance may play an important role in pathogenesis of AA and regulating the balance of IL-18 and IL-18BP may be a therapeutic approach to AA.</p>

Secretion of IL-18 and IL-18 binding protein from splenocytes of ITP patients in vitro / 中国实验血液学杂志

This study was aimed to investigate the expression and clinical significance of IL-18, IL-18 binding protein (IL-18BP), IFN-γ and IL-4 secreted from splenocytes of patients with idiopathic thrombocytopenic purpura (ITP) in vitro. Spleen mononuclear cells (MNC) were prepared by using routine sterile method, and were cultured in RPMI 1640 complete medium containing 10 µg/ml PHA, 10% fetal calf serum at 37°C and 5% CO2. The levels of IFN-γ, IL-4, IL-18 and IL-18BP secreted from MNC of ITP patients and normal controls were determined after culture for 48 hours. The results showed that after culture of spleen MNC for 48 hours, the levels of IL-18 and IFN-γ were significantly higher in patients with ITP than that in controls, but the levels of IL-18BP was not significantly elevated in ITP patients. The level of IL-4 was below the detectable limit of the assay used. It is concluded that imbalance between IL-18 and IL-18BP may play an important role in pathogenesis of ITP, and regulation of balance between IL-18 and IL-18BP may be a therapeutic approach against ITP.

The role of interleukin-18 and interleukin-18 receptor in predominant Th1 immune response of patients with immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the role of interleukin (IL)-18 and IL-18 receptor (IL-18R) in the predominant Th1 type cytokine response in patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Fifteen patients with active phase ITP, eighteen in remission and thirteen healthy controls were enrolled in this study. T-bet and GATA-3 mRNA levels in peripheral blood mononucleated cells (PBMNC) were measured by reverse transcriptase polymerase chain reaction (RT-PCR); the plasma IL-18 level by enzyme linked immunosorbent assay (ELISA), the expression of IL-18R on CD3(+) lymphocytes and total lymphocytes by flow cytometry(FCM).</p><p><b>RESULTS</b>The T-bet mRNA levels in patients with active phase ITP was 3.572 fold as much as that in the controls (P < 0.05), while the GATA-3 mRNA levels were 0.378 fold of that in controls (P < 0.05). The levels of plasma IL-18 and IL-18R on CD3(+) lymphocytes were significantly increased in active phase ITP than in remission phase and controls. There was no difference in ratio of T-bet/GATA-3 between remitted ITP and controls and so was for T-bet mRNA, GATA-3 mRNA, plasma IL-18 and IL-18R on CD3(+) lymphocytes.</p><p><b>CONCLUSION</b>ITP as a disease of Th1-dominant response there is an unbalance between T-bet and GATA-3 in its active phase; IL-18 and IL-18R being upregulated.</p>