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Identifier

000375965

Title

Abnormal telomere shortening in PBMCs and granulocytes of patients with CIN

Alternative Title

Μη φυσιολογική βράχυνση των τελομερών των λεμφομονοπυρήνων και κοκκιοκυττάρων του περιφερικού αίματος σε ασθενείς με χρόνια ιδιοπαθή ουδετεροπενία

Author

Pavlaki, Konstantia

Author

Παυλάκη, Κωνσταντία

Thesis advisor

Παπαδάκη, Ελένη

Reviewer

Κρετσοβάλη, Ανδρονίκη

Abstract

Background: Abnormal telomere shortening in peripheral blood mononuclear cells (PBMCs) and/or granulocytes has been reported in patients with acquired bone marrow failure syndromes, including aplastic anaemia, myelodysplasia syndromes and paroxysmal nocturnal haemoglobinuria. The abnormality has been mainly attributed to the rapid turnover of haemopoietic progenitor cells in an attempt to compensate for the marrow failure. Aims: To evaluate the telomere length of PBMCs and granulocytes in patients with chronic idiopathic neutropenia (CIN). CIN is an acquired disorder of granulopoiesis characterized by increased apoptosis of the granulocytic progenitor cells and presence of activated T-lymphocytes in the peripheral blood and bone marrow. Methods: We studied 40 patients with CIN (males n=8, females n=32) aged 30 to 72 years, (median 49 years) and 66 healthy individuals (males n=13, females n=53) aged 30 to 74 years (median 44 years). DNA was extracted from peripheral blood granulocytes and PBMCs and telomere length was evaluated by means of real time PCR using β-globin as control single copy gene. Individual telomere length was reflected by the relative telomere/single-copy-gene (T/S) ratio based on the formula T/S=2-ΔCt (Ct= Cttelomere- Ctβ-globin), in both cell populations tested. Results: Individual T/S ratio in the group of patients was characterized as appropriate or inappropriate for a given age by defining the observed/predicted (O/P) relative telomere length ratio for each cell population (granulocytes or PBMCs) on the basis of the equation derived from the linear regression analysis of the correlation between T/S ratio and age (years) of the controls. We found that the mean O/P telomere length ratio of patient PBMCs (0.768 ± 0.562) was out of the lower 95% confidence limit of healthy controls (mean O/P telomere length ratio 1.053 ± 0,36; p= 0,0092), suggesting inappropriate telomere loss by age in CIN patients. In accordance with the PBMCs, the granulocytes’ mean O/P ratio (0.628±0.045) was out of the 95% confidence limit of the controls (0.999±0.106; p=0.0165), suggesting inappropriate granulocyte telomere loss in CIN patients. Finally, no association was found between absolute neutrophil counts and granulocyte T/S values in the group of CIN patients. Summary/Conclusions: Patients with CIN display inappropriate telomere loss in PBMCs compared to age- and sex- matched healthy individuals. This abnormality might be attributed to the increased activation of peripheral blood T-lymphocytes previously described in CIN. The granulocytes of CIN patients display an ageindependent telomere length. Overall, these data indicating inappropriate telomere loss in PBMCs and granulocytes of patients with CIN, support further the hypothesis that CIN shares common pathophysiologic features with other acquired bone marrow failure syndromes.

Language

Greek

Subject

Granulocytes

Neutropenia

Telomeres

Κοκκιοκύτταρα

Τελομερή

Χρόνια ιδιοπαθής ουδετεροπενία

Issue date

2010-12-14

Collection