Telomerase Activity in Myeloid Leukaemias

Abstract

melomeres are unique structures at the end of the W'chromosomes necessary for chromosomal integrity and overall genomic stability. Human telomeres are composed of a hexameric sequence (TTAGGG) repeated for many kilobases. As cells divide, telomeres continuously shorten with successive cell division due to the inability of normal DNA polymerases to replicate the end of linear molecules. So telomere shortening was ascribed a function, i.e. to act like a mitotic clock that counts the number of cell divisions and limits endless cell proliferation by signaling entry into senescence.

The ribonucleoprotein telomerase, provides the necessary enzymatic activity to restore and maintain telomere length. Telomere utilizes its associated functional RNA component as a template for catalyzing DNA addition at the telomeres. Because most normal cells that senesce undergo telomere shortening due to lack of telomerase activity (TA), telomere attrition has been proposed as an important component of cellular aging. If however, cancer promoting genetic mutations block Issuance of safety signals that prevent the cells from dividing further, cells will bypass normal senescence and continue to divide. They will also presumably continue telomeric sequences and to undergo chromosomal alterations that allow further possibly carcinogenic mtutations to arise. If the genetic derangements lead to the manufacture of telomerase, cells will not completely lose their telomere and the shortened telomere will be rescued.