ASTUDY OF TELOMERASE ACTIVTTY IN PERIPHERAL BLOOD CELLS IN TREATED AND UNTREATED CHRONIC MYELOGENOUS LEUKEMIA PATIENTS

Abstract

Deoxyribonucleic Acid (DNA) is normally the primary form in which genetic inform,. ation is stoi-ed and from which it is passed to daughter cells' by replication. The nucleus of eukaryotic cells contains several or many nuclear chromosomes, each chromosome contains one

very large DNA molecule (Lewin, 1974).

Telomeres are the physical ends of eukaryotic chromosomes. Telomeric DNA sequences are highly conserved in all well-characterized eukaryotic nuclear chromosomes, and differ greatly from the termini of linear viral, extra-nuclear plasmiu, or mitochondrial DNA Human te1omeric DNA consists of 2-15 kb of ta.D.dem1y-repeated sequences (TTAGGG)n oriented 5'-3' towards the end of the chromosome. The evolutionary conservation of this repetitive DNA sequence implies that these sequences are essential to cellular function (Yamada, 1996).

These repeated sequences are synthesized by a ribonucleoprotein ' enzyme 'telomerase', which• is composed of RNA and a few proteins.

Te1omerase adds hexameric repeats of•5'-TTAGGG-3' to the end of mammalian chromosomal DNA (telomeres) to compensate for the progressive loss that occurs with successive rounds of DNA replication (Sharma et al., 1996).

It has been proposed that telomeres shorten with every cell cycle because the nonnal mechanism of DNA replication carmot replicate the end sequences of tl1e lagging DNA strands (Pan et al., 1997). On the other hand, telomeres provide important protection to avoid loss of master genes that may exist at subtelomeric regions. Moreover, erosion of teloineres by cell replication results in telomeric-associated cytogenetic aberrations (Ohyashiki et al., 1997).