Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities.

INTRODUCTION: In acute myeloid leukemia (AML), it has been shown that AML-derived cells often remain sensitive to autophagy-inducing stimuli, leading to the idea that harnessing the autophagy can be pertinent to AML cytotoxic therapy. Despite this promising notion, to date, there is no comprehensive study addressing autophagy-related genes expression status in AML. As a critical mediator, BECN1 influences the onset and advance of autophagy and several studies have pointed to the BECN1 recurrent allelic deletion and expression variation in a broad range of tumors. To explore this caveat, we chose this alteration-prone gene to investigate in our study. METHODS: We have analyzed the expression status of BECN1 in a series of 128 de novo AML patients using real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: In our favorable subgroup, BECN1 expression did not alter (P = 0.301), but in intermediate and unfavorable patients, we have had BECN1 low expression compared to the normal controls (P = 0.008 and P < 0.001, respectively). We found evidence for the association of reduced expression of BECN1 with FLT3-ITD mutation (19 of 27 patients), monosomal karyotype (all of 11 patients), higher age, and WBC count. CONCLUSION: Overall, remarkable association of reduced expression of BECN1 with FLT3-ITD mutation and monosomal karyotype and their functional relationship is interesting which should be addressed and verified in future studies.

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis patients.

Resistance to recombinant erythropoietin (rEPO) in hemodialysis patients may be due to inadequate iron recruitment and defect in iron use. In this cross over randomized clinical trial, 30 hemodialysis patients with serum ferritin levels of ≥500 ng/ml, hemoglobin ≤11.0 g/dl, and transferrin saturation (TSAT) of 20% or less were administrated intravenous iron (50-100 mg/wk) and rEPO (120-360 U/kg/wk) for 6 months. Patients were excluded if there was a clear explanation for rEPO hyporesponsiveness. Patients were divided into two groups. Group1 received standard care and 500 mg of intravenous ascorbic acid (IVAA) with each dialysis session in the first week of each month for a total of 3 months. Group 2 received standard care only. After 2 month washout period, groups were crossed over. Each month hemoglobin (Hb) was assessed. Iron, TIBC (transferrin iron binding capacity), TSAT, iPTH (intact parathyroid hormone), liver enzymes, albumin and cholesterol levels were measured every 3 months. After 3 months of intervention, Hb significantly increased from 10.11 to 12.19 g/dl (P <0 0.001; 95% confidence interval [CI] 2.7-1.4) and TSAT increased from 18.9 to 28.1% (P = 0.008; 95% CI 0.09-3), while ferritin and serum iron declined significantly from 1391 to 938 ng/ml (P = 0.001; 95% CI 216-689), 97.2 to 64.6 (P = 0.001; 95% CI 14.8-50.4) in the study group. Change of Hb over time in IVAA group was significant (P < 0.0005). There were significant differences between two groups in change of Hb level over time (P < 0.0005) and treatment effect (P = 0.002). Baseline laboratory tests were similar in the two groups and there was no carry over effect at phase 2. We showed that low amount of IVAA could reduce ferritin level and enhance Hb and TSAT, suggesting improved iron utilization.

Hyperhomocysteinemia after kidney transplantation.

OBJECTIVE: To determine the prevalence of hyperhomocysteinemia (plasma homocysteine[Hcy] concentration≥15 µmol/L) and evaluate its correlation with allograft function. MATERIALS AND METHODS: The study included 159 stable renal transplant recipients (104 men and 55 women). The prevalence and severity of hyperhomocysteinemia were compared in the transplant recipients vs 72 patients (48 men and 24 women) receiving hemodialysis therapy. RESULTS: The mean (SD; range) fasting total Hcy concentration was higher in the hemodialysis group compared with the renal transplantation group: 27.4 (18.3; 10-95) µmol/L vs 16.6 (9.5; 4.5-45.0) µmol/L (P=.00). Hyperhomocysteinemia occurred more frequently in patients receiving hemodialysis therapy (74% vs 49%). No significant correlation was observed between Hcy concentration and recipient sex, cyclosporine trough concentration and concentration at 2 days after dosing, dyslipidemia,cytomegalovirus infection, diabetes mellitus, or aspartate or alanine aminotransferase concentration. Multivariate regression analysis revealed that serum creatinine concentration (P=.02) was the major determinant of increased total Hcy concentration in renal transplant recipients. CONCLUSION: A high prevalence of moderate hyperhomocysteinemia was observed in renal transplant recipients. There was no correlation between graft function and Hcy concentration.