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.
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