Telomeres and Telomerase in Normal and Malignant Haematologic Cells

Telomeres, the ends of eukaryotic chromosomes are structural and functional units composed of proteins and repetitive DNA sequences. Telomeres protect the ends of chromosomes from DNA loss caused by incomplete replication of 3' ends. The obligatory loss of terminal sequence with each cell division leads to telomere shortening, and is counteracted in germline cells by an enzymatic activity termed telomerase that resynthesizes telomeric DNA de novo. Telomere length and telomerase activity have been measured by several groups in both normal and malignant blood and marrow cells. Telomere length decreases with age in normal blood and bone marrow, despite the presence of a detectable telomerase activity. In most hematologic malignancies telomere length is short and telomerase activity is enhanced, compatible with the late activation of the enzyme in tumour development. The implications of these findings for tumour pathogenesis, diagnosis, and treatment are discussed.