Human chromosome ends are capped by telomeric DNA composed of long
arrays of (TTAGGG)n repeats. During each cell division, telomeric DNA is shortened
by 50-100 bp. This attenuation of chromosome ends results in a loss of coding
sequences and end-to-end chromosomal fusions, leading to chromosomal instability and
aberrations. Therefore, telomere shortening is a critical event that acts as a mitotic clock
to measure cellular life span. Telomerase, a ribonucleoprotein composed of a catalytic
subunit (TERT), an RNA template (TERC), and the dyskerin protein, elongates
telomeric sequences in germ cells and immature precursors such as hematopoietic stem
cells. Telomerase is activated by multiple signaling pathways and its activity is
regulated at the levels of gene transcription and translation, as well as post-translational
modifications, trafficking, and assembly of the protein. Telomerase is upregulated in
most cancer cells, including hematologic malignancies. Telomere shortening and
telomerase activation are correlated with the prognosis and aggressiveness of various
hematologic tumors. Therefore, targeting telomerase may be an attractive therapeutic
strategy for hematologic malignancies. In fact, several strategies of telomerase
inhibition, such as G-quadruplex-interacting agents, catalytic/reverse transcriptase
inhibitors, oligonucleotides, and immunotherapy, have been developed as therapeutic
methods.
Keywords: Acute leukemia, chronic leukemia, hematologic malignancies,
malignant lymphoma, multiple myeloma, regulation mechanism, shelterin
complex, signal transduction, telomerase, telomerase inhibitor, telomere.
