Telomerase activity and telomere length in AML-M3 patients

The telomeric DNA together with its associated proteins protects the chromosome ends from degradation or aberrant recombination. Telomerase and telomere are closely associated with development of cancers. In this study we aim to investigate the significance of telomerase activity (TA) and telomere length (TL) in patients with acute promyelocytic leukemia (APL). Peripheral blood samples were taken from 20 APL patients during the diagnosis and from 25 healthy normal individuals at different age ranges. Telomerase activity (TA) was assessed by TRAP- ELISA and -PAGE procedures. Genomic DNA isolated from patient mononuclear cells was digested with Rsa1 and Hinf1 restriction enzymes; electrophoresis was performed in 0.8% agarose gels, and telomere length (TL) was determined by southern analysis using a Chemiluminescence-based assay. As oppose to the normal individuals, telomerase activity was detected in peripheral blood mononuclearcells of all APL patients (P<0.001). Marked differences were observed in the sizes of the telomere length in the normal blood cells and APL leukemic cells. The leukemic cells of 18 of 20 (90%) patients with APL showed a significant reduction in the length of telomeric DNA, ranging from 2.3 to 6.7 kbp (median 3.5 kbp), while the telomere length in healthy normal individuals was 9.1 to 14.8 kbp (median 11.6 kbp) (P<0.000). In healthy individuals, the average TL was found to vary with age, and the rate of telomere shortening was age dependent. Telomere length shortening and Telomerase up-regulation are closely associated with acute promyelocytic leukemia; therefore, they may be used as potential markers for diagnostic, prognostic and for therapeutic intervention in APL patients.