Correlation of telomerase activity to apoptosis and survival in adult acute lymphoblastic leukemia: an Egyptian single-center study.

Telomerase is activated in most tumors, but suppressed in normal human somatic cells. Current evidence indicates that telomerase reactivation is a critical step in carcinogenesis, with a close relationship to apoptosis. The goal of this study was to investigate the levels and relationship of telomerase activity to apoptosis and its impact on the survival of Egyptian adult acute lymphoblastic leukemia patients. Telomerase activity was quantified by polymerase chain reaction (PCR) and detected by enzyme-linked immunosorbent assay (ELISA), while apoptosis was measured at the single-cell level by fluorescence in situ detection using flow cytometry in 15 control subjects and 40 acute lymphoblastic leukemia (ALL) patients at presentation. Telomerase activity in ALL patients was negatively correlated to apoptosis [percent and mean fluorescence intensity (MFI)] (p < 0.001 for percent and p < 0.001 for MFI) and to the 4-year survival rate (p < 0.05), to which apoptosis (percent and MFI) was consequently positively correlated (p < 0.001 for percent and p < 0.05 for MFI). For telomerase, the highest positive predictive value (PPV) for mortality (93.3%) was at a cut-off value of 13 amol/ml, while those for apoptosis (85% for percent of apoptotic cells and 90.9% for MFI) were at a cut-off of 8% and 0.19 MFI. This makes the measurement of telomerase activity in ALL patients a potential tool to predict disease with unfavorable outcome and a candidate tumor marker.

Acetylator phenotyping in patients with malignant lymphomas, using caffeine as the metabolic probe.

OBJECTIVE: The study was designed to answer the question whether a particular (slow/fast) acetylator phenotype is a risk for malignant lymphoma patients. Differences in acetylator phenotypes were previously described in urinary bladder and colorectal carcinoma patients compared to controls. Addressing this issue may help understanding the possible role of xenobiotics' metabolism in the pathogenesis of malignant lymphomas. Caffeine is currently preferred as a metabolic probe due to its noninvasiveness. DESIGN: Case-control study. SETTING: Hematology/oncology inpatient unit and outpatient clinic, Ain Shams University Hospitals, Cairo, Egypt: a tertiary care academic medical institution. PARTICIPANTS: Urine samples were collected 4 h after the oral administration of a caffeine-containing beverage to 83 patients with malignant lymphomas and 92 control subjects. Diagnosis of lymphoma was ascertained histopathologically. Controls were matched in terms of age, sex and residence (urban/rural). MEASUREMENTS: To define the acetylation phenotype, the nanomolar ratio of the urinary concentrations of the caffeine metabolites: acetylamino-6-amino-3-methyluracil and 1-methylxanthine (AAMU/1X) was calculated for every study subject. RESULTS: An excess of fast acetylators was shown in the malignant lymphoma group compared to the control. The odds ratio for malignant lymphoma associated with fast acetylation was 1.304 (95% CI, 0.709-2.398; p = 0.439). Paradoxically, an excess of the slow acetylator phenotype was observed in patients with low-grade non-Hodgkin lymphoma (n = 25) compared to other subjects of the lymphoma group. The odds ratio for low-grade lymphoma associated with slow acetylation was 4.00 (95% CI, 1.316-12.155; p = 0.014). CONCLUSIONS: Owing to the small sample size, the association between the acetylator phenotype and malignant lymphomas could not be excluded. However, the study suggests that, compared to other types of lymphoma, low-grade non-Hodgkin lymphoma would be associated with slow acetylator phenotype.