Abnormal glucose tolerance in beta-thalassemia patients: possible risk factors

In beta-thalassemia major, transfusional iron overload lead to impaired glucose tolerance [IGT] then diabetes mellitus [DM]. The pathogenetic mechanisms leading from siderosis to diabetes are still poorly understood. To assess the glycometabolic status in transfusion-dependent Egyptian beta-thalassemia patients and to evaluate the possible risk factors for abnormal glucose tolerance [AGT] in them. Oral glucose tolerance test [OGTT] was done to 54 multi-transfused thalassemic patients, aged 10.1-25.1 years, and 28 age-matched normal controls with measuring serum insulin level at 0, 120 minutes. Insulin sensitivity and insulin release index were calculated according to the homeostasis model assessment [HOMA], fasting insulin glucose ratio [FIG], insulin sensitivity index for glycemia [ISl gly] and fasting insulin resistance index [FIRI]. Indicator of iron overload and liver status were recorded. Thirteen patients [24.1%] were diagnosed to have variable degrees of AGT; either DM in 6 cases [11.1%] or IGT in 7 cases [13%] and normal glucose tolerance [NGT] was in 41 patients [75.9%]. Cases with AGT had significant higher mean postprandial insulin, FIRI and HOMA insulin resistance [IR], p=0.0001 for all, and significant lower mean HOMA beta-cell, p=0.007 if compared to the cases with NGT. By stepwise logistic regression analysis, the total blood taken per year was the independent risk factor for abnormal glucose tolerance, OR=0.49, p=0.03. Serum ferritin was higher in cases with AGT compared to cases with NGT, p= 0.04 and it correlated with fasting insulin level, FIRI and HOMA IR, p=0,003,0.001, 0.001 and r=0.4, 0.5, 0.5 respectively. Chronic hepatitis C was detected in 12 patients [92.3%] with AGT. Abnormal glucose tolerance is common in multi-transfused beta-thalassemia patients, which could be attributed to impaired beta-cell function, along with insulin resistance

association and clinical impact of PRAME mRNA expression in acute leukemias

PRAME [preferentially expressed antigen of melanoma] has been previously Identified as a melanoma antigen. It encodes an antigen recognized by autologous cytotoxic T lymphocytes. It shows no or very low expression in normal tissues, however a wide range of tumors including haemato-poietic neoplasias express this gene. The aim of this study is to detect PRAME gene expression in acute leukemias and to evaluate its clinical importance. Study and control groups consisted of thirty newly diagnosed cases of acute leukemia [15 AML and 15 ALL cases] and 10 age-matched healthy persons respectively. PRAME mRNA was detected by RT-PCR. Cases were monitored for 6 months and their treatment outcome was classified into responders and non responders. Initially PRAME positive responders were selected for re-evaluation of their PRAME expression by RT-PCR. Cases results in first admission showed that 50% of the studied leukemia cases expressed PRAME of which 66.7% AML cases and 33.3% ALL cases. Although the expression of PRAME was higher in AML than ALL, however the difference was not statistically significant. In particular PRAME was frequently expressed in AML M2 [40%], AML M3 [30%] and ALL L2 [80%], All normal controls did not express any PRAME mRNA transcript. The difference between patients and controls was statistically significant [p=0.00]. NO important correlation was found between PRAME expression, clinical and laboratory data such as age, sex, organomegally, lymphadenopathy, HB and blast%. As regards treatment outcome, PRAME positive cases were consistent more with poor outcome, although statistical companson of both groups did not reach statistical significance. BY reanalyzing PRAME expression in PRAME positive responders [5 cases], it was found that all cases still expressed PRAME mRNA transcript with the exception of one case. Hence a future possibillty to use PRAME as a marker to verify molecular remission and/or predict haematological remission/relapses should be particularly considered. Monitoring the levels of PRAME expression during the course of disease progression is absolutely indicated to postulate its potential as a marker for minimal residual disease. The impact of different treatment approaches on the levels of PRAME expression needs further investigations on a wider scale