oa Molecular Diagnosis and Vaccines - Telomere length and telomerase activity in acquired aplastic anemia

Volume 3, Issue 1
  • ISSN : 1687-2010



In most human cells , the average length of telomere repeats at the ends of chromosomes provides indirect information about their mitotic history, and in haematopoietic stem cells it may serve as an indicator of hematopoietic ageing. Telomere length (TL) is maintained by a balance between replication rate and telomerase activity. The aim of this study is to explore telomere length and telomerase activity and their association with the clinical severity in patients with acquired aplastic anemia (AA) and to correlate them with the clinical factors of the disease. Thirty one cases with acquired AA were studied. They included eight cases with severe AA (sAA) (5 males and 3 females , their mean ages 7.1 0.8 years), 13 cases with moderate AA (mAA) (8 males and 5 females, their mean ages 7 0.7 years ) and 10 cases in complete remission (CR) (6 males and 4 females, their mean ages 7.2 0.6 years), were studied. Ten age and sex matched healthy children were taken as control group. .All patients were subjected to through history taking , clinical examination,complete blood picture, bone marrow aspiration and/or biopsy, measurement of Telomere length by flowcytometry using fluorescent in situ hybridization and fluorescin conjugated PNA probe and measurement of Telomerase activity (TA) by PCR-ELISA technique. The results of this study revealed significant decrease in telomere length in cases of AA than that of controls (p<0.001). The TL in sAA and mAA was significantly decreased compared with that of normal controls. Moreover, TL in patients with sAA was significantly shorter than patient with mAA(p<0.02). The TL in CR also tended to be shorter than that of normal controls, although the difference was not statistically significant. Telomerase activity was significantly high in patients with aplastic anemia (p<0.001). A positive correlation was found between absolute neutrophil count (ANC), hemoglobin (Hb), platelet count and TL(p<0.001), while negative correlation between these parameters and TA was found. Inverse correlation was observed between TL and TA (P<0.001). Our findings suggest that haematopoietic stem cells in patients with AA rapidly lose telomere length and show elevated telomerase activity. The telomere shortening further accelerated, while telomerase activity further reduced depending on the severity of stem cell pool contraction. Defective telomerase suggests that treatments directed at correction of telomerase activity might benefit patients who do not respond to conventional therapy. Further studies of telomere length and TA are needed to address the relationship with late clonal disorders and for the development of new therapeutic protocol for the disease.

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