T-cell CD38 expression in B-chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a heterogeneous disease with some patients having an indolent course never needs treatment, while others having rapidly progressive one requires intensive treatment. In recent decades, numerous prognostic markers, such as immunoglobulin variable region heavy-chain (IgVH) mutational status, ZAP-70 and the expression of CD38 on leukaemic cells were introduced to screen for patients likely to have progressive course of B-CLL bearing the potential to facilitate risk-adapted treatment strategies. In B-CLL, T cell function is shown to be dysregulated. CD38 has been demonstrated to be an important transmembrane signalling molecule of T cell with a direct effect on its function. The present study was conducted to analyse CD38 expression on T cells by flow cytometry to evaluate its impact on the clinical course of 88 unselected B-CLL patients and correlate it with other risk factors. CD38 expression level on T cells was shown to predict the clinical course of B-CLL in male patients but not in female patients. Male patients showed CD38 expression on T cells in a stage-dependent manner, in contrast to female patients who showed higher expression irrespective to clinical staging. CD38 expression on T cells negatively interacted with treatment-free survival in male patients. Multivariate analysis revealed that CD38 expression level on T cells is an independent prognostic factor in B-CLL male patients. Simultaneous evaluation of CD38 expression on both B-CLL cells and T cells allowed predicting male patient groups with the most favourable prognosis as well as those with the worst.

Prognostic implication of N-RAS gene mutations in Egyptian adult acute myeloid leukemia.

The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. Point mutations of the N-RAS gene are the most frequent somatic mutations causing aberrant signal-transduction in acute myeloid leukemia (AML). The aim of the present work is to study the frequency and prognostic significance of N-RAS gene mutations (N-RASmut) in de novo Egyptian adult AML. Bone marrow specimens from 150 patients with de novo acute myeloid leukemia and controls were analyzed by genomic PCR-SSCP at codons 12, 13 (exon 1), and 61 (exon 2) for N-RAS mutations. In 12.7% (19/150) AML cases, N-RAS gene mutations were found and were observed more frequently in the FAB subtype M4eo (P = 0.028) and with codon 12, 13 (14 of 19; 73.7%). Patients with N-RAS mutation had a significant lower peripheral and marrow blasts (P = 0.004, P = 0.03) and clinical outcome did not improve more than in patients without mutation. In patients with N-RAS gene mutation vs. those without, complete remission rate was (63.2% vs. 56.5%; P = 0.46), resistant disease (15.8% vs. 23.6%; P = 0.51), three years overall survival (44% vs 42%; P= 0.85) and disease free survival (42.1% vs. 38.9%, P = 0.74). Multivariate analysis showed that age was the strongest unfavorable factor for overall survival (relative risk [RR], 1.9; P = 0.002), followed by cytogenetics (P = 0.004). FAB types, N-RAS mutation and leukocytosis were the least important. In conclusion, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML.

Relationship between insulin resistance and some coagulation and fibrinolytic parameters in patients with metabolic syndrome.

BACKGROUND: Insulin resistance syndrome has been shown to be associated with many coagulation and fibrinolytic proteins, and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders. This study was conducted to determine the levels of some of the hemostatic parameters in subjects having metabolic syndrome and to correlate these values with the anthropometric and metabolic variables associated with this syndrome. SUBJECTS AND METHODS: The participants were 46 obese nondiabetic subjects, 28 (group 1) who fulfilled the Adult Treatment Panel III criteria of the metabolic syndrome and 18 (group 2) who did not have metabolic syndrome, and a control group of 14 lean subjects (group 3) of matched age and sex. Clinical and laboratory evaluation of the study groups focused on anthropometric measurements (weight, height, body mass index, waist circumference, and sagittal abdominal diameter), blood pressure, and laboratory measurements of fasting plasma glucose, fasting insulin, serum lipids, tissue plasminogen activator (t-PA), antithrombin III activity (AT III), protein C, and von Willebrand factor (vWf) antigen. RESULTS: We observed significant increase in the concentrations of t-PA and vWf antigens in subjects having metabolic syndrome (group 1) compared to the other groups, along with nonsignificant changes in the levels of protein C antigen and AT III activity. Both t-PA and vWf showed significant correlation with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) as a measure of insulin sensitivity. t-PA concentrations showed significant correlations with most of the variables associated with metabolic syndrome, including waist circumference, body mass index, systolic blood pressure, fasting plasma glucose, fasting insulin, and high-density lipoprotein cholesterol. On the other hand, vWf showed significant correlations with fasting plasma glucose, fasting insulin, and sagittal abdominal diameter, with nonsignificant correlations with the other variables. CONCLUSION: Hemostatic and fibrinolytic parameters should be included in characterization of the insulin resistance syndrome. t-PA and vWf-antigen concentrations were increased in subjects with metabolic syndrome and correlated with the HOMA-IR measure of insulin sensitivity. Because both t-PA and vWf are mainly released from vascular endothelium, these findings could be an indicator of endothelial dysfunction in subjects with insulin resistance and metabolic syndrome.