Resveratrol accelerates erythroid maturation by activation of FoxO3 and ameliorates anemia in beta-thalassemic mice.

Resveratrol, a polyphenolic-stilbene, has received increased attention in the last decade due to its wide range of biological activities. Beta(ß)-thalassemias are inherited red cell disorders, found worldwide, characterized by ineffective erythropoiesis and red cell oxidative damage with reduced survival. We evaluated the effects of low-dose-resveratrol (5 µM) on in vitro human erythroid differentiation of CD34(+) from normal and ß-thalassemic subjects. We found that resveratrol induces accelerated erythroid-maturation, resulting in the reduction of colony-forming units of erythroid cells and increased intermediate and late erythroblasts. In sorted colony-forming units of erythroid cells resveratrol activates Forkhead-box-class-O3, decreases Akt activity and up-regulates anti-oxidant enzymes as catalase. In an in vivo murine model for ß-thalassemia, resveratrol (2.4 mg/kg) reduces ineffective erythropoiesis, increases hemoglobin levels, reduces reticulocyte count and ameliorates red cell survival. In both wild-type and ß-thalassemic mice, resveratrol up-regulates scavenging enzymes such as catalase and peroxiredoxin-2 through Forkhead-box-class-O3 activation. These data indicate that resveratrol inhibits Akt resulting in FoxO3 activation with upregulation of cytoprotective systems enabling the pathological erythroid precursors to resist the oxidative damage and continue to differentiate. Our data suggest that the dual effect of resveratrol on erythropoiesis through activation of FoxO3 transcriptional factor combined with the amelioration of oxidative stress in circulating red cells may be considered as a potential novel therapeutic strategy in treating ß-thalassemia.

Analysis of overexpression of vascular endothelial growth factor-C in patients with angioimmunoblastic T-cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the vascular endothelial growth factor-C (VEGF-C) expression and its clinical significance in malignant lymphoma.</p><p><b>METHODS</b>Lymphoma cells were isolated by laser microdissection. VEGF-C expression in lymphoma tissue and microdissected lymphoma cells was measured by realtime quantitative PCR. Meanwhile, vessel ultrastructure was identified by transmission electron microscopy.</p><p><b>RESULTS</b>Comparing with that in 8 patients with reactive lymphocyte hyperplasia, VEGF-C was overexpressed in angioimmunoblastic T-cell lymphoma, both in lymphoma tissue (n = 18, P = 0.0020) and in microdissected lymphoma cells (n = 10, P < 0.0001). Increased VEGF-C level was associated with bone marrow infiltration (P = 0.0039), skin involvement (P = 0.0046) and high-risk international prognostic index (P = 0.0302). In VEGF-C overexpressed cases, ultrastructural study showed dystrophic vessels, with swelling endothelial cells and absence of pericytes.</p><p><b>CONCLUSION</b>The value of VEGF-C expression might be a biomarker of disease progression in angioimmunoblastic T-cell lymphoma.</p>

BCL-XL expression and mutation in non-Hodgkin's lymphoma / 中国实验血液学杂志

The study was aimed to investigate the BCL-XL expression and mutation, and its clinical significance in non-Hodgkin's lymphoma. Lymphoma cells were selectively isolated by laser microdissection. BCL-XL expression from lymphoma tissue and microdissected lymphoma cells was measured by using real-time quantitative reverse transcription-polymerase chain reaction. BCL-XL mutation was analyzed by using direct sequencing of PCR products. The results showed that compared to 15 patients with reactive hyperplasia, BCL-XL was overexpressed in follicular lymphoma (n = 30), both in lymphoma tissue (P = 0.0064) and in microdissected lymphoma cells (P < 0.0001). No significant rise of BCL-XL expression was observed in patients with T-cell lymphoma (n = 24) and diffuse large B cell lymphoma (n = 24). In follicular lymphoma, high BCL-XL level was associated with multiple extranodal involvement (P = 0.0004), elevated lactate dehydrogenase level (P = 0.0019), high-risk international prognostic index (P = 0.0013) and a short overall survival time (P = 0.0451). Mutation analysis revealed one synonymous mutation (Codon 109 ACA-->ACC) in one case of follicular lymphoma patient. It is concluded that BCL-XL expression is closely correlated with progress of follicular lymphoma and prognosis of patients with follicular lymphoma. The value of BCL-XL expression as a prognostic marker in follicular lymphoma should be considered.