Telomere and Stem Cell Biology in Chronic Myeloid Leukemia

The measurement of telomere length in peripheral blood cells can give an insight into the replicative history of their respective precursor cells, the hematopoietic stem cells (HSC). Much of the observed telomere loss occurs at the stem and progenitor cell level even though these populations express the enzyme telomerase. Investigations in normal steady state hematopoiesis provided the basis for follow up studies in model disorders with increased turnover rates of HSC either due malignant transformation or due to depletion of the stem cell compartment like in defined bone marrow failure syndromes or as a consequence of reduced bone marrow reserve e.g. due to chemotherapy-induced hematological toxicity. In model scenarios like in Chronic myelogeneous leukemia (CML), the degree of telomere shortening can be correlated both with disease duration, disease stage and severity as well as with response to disease-modifying treatment strategies. Whether alterations in telomere biology are secondary phenomena or play a causal role for replicative senescence and/or the induction of genetic instability linked to disease progression in these acquired HSC disorders is under investigation.

Keywords: Telomere; Telomerase; stem cell; chronic myeloid leukemia