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Identifier

000447551

Title

Προσδιορισμός μήκους τελομερικών άκρων σε παιδιά, εφήβους και νεαρούς ενήλικες με οξεία λεμφοβλαστική λευχαιμία

Alternative Title

Determination of telomeres length in children ,teens and young adults, with Acute Lymphoblastic leukemia

Author

Βακωνάκη, Ελένη

Thesis advisor

Στειακάκη, Ευτυχία

Reviewer

Τσατσάκης, Αριστείδης
Τζατσαράκης, Εμμανουήλ

Abstract

Acute Lymphoblastic Leukemia is a blood malignancy characterised by rapid and excessive production of abnormal precursor white blood cells. It is the most common neoplasm in childhood, accounting for 80% of childhood malignancies, with an excellent prognosis, as more than 90% of pediatric patients can be cured. In about 90% of Acute Lymphoblastic Leukemia cases numerical chromosomal abnormalities as well as structural abnormalities such as permutations, deficiencies etc. resulting in disruption of the expression of genes involved in hematopoiesis can be detected. As a result cells proliferate uncontrollably, leading the cell to rapid cell aging. The term cell aging indicates the state of irreversible cessation of cell proliferation resulting in the accumulation of continuous damage to the genetic material, ultimately leading to carcinogenesis. The chromosomes telomeres have a protective role, preserving the chromosome integrity and offering protection from degradation, recombination and fusion. The length of the telomere limbs depends on the cell type, the age of the individual, as well as the person's state of health and habits. This reduction takes place in each cell division until it reaches the Hayflick limit where the cell is led to apoptosis. The aim of this study was to determine the degree of cellular aging in patients with Acute Lympoblastic Leukemia and to determine whether the telomere length measurement could be a biomarker of the disease severity, the response to treatment, the risk of relapse and ultimately the survival of patients. The study included a total of 35 children, adolescents and young adults, aged from 1.5 to 18 years, diagnosed with Acute Lymphoblastic Leukemia during the period 1/1/2010 to 31/12/2020 at the Department of Pediatric Hematology/ Oncology of the University Hospital of Crete. 62.9% of the patients were males and the rest females. Regarding the type of Acute Lymphoblastic Leukemia, 88.6% was diagnosed with B lineage Acute Lymphoblastic Leukemia and the remaining with T-lineage ALL. In each patient two samples were collected from the bone marrow, the first at diagnosis and the other when was achieved. DNA was extracted and concentration and purity were measured by photometry. The length of the telomeres was determined by qPCR methodology. Statistical analysis using t-test and ANOVA followed. Our results showed that the mean length of telomeres in the lymphoblast specimens obtained at the diagnosis was 2.18 ± 1.04 Kb while at the time of remission the mean length was higher, 4.18 ± 1.54 Kb. Two of the patients showed longer telomere lengths in lymphoblasts compared to normal lymphocytes at remission. One of the patients had absolutely no difference in the mean telomere length between the two samplings and is the only one patient with disease relapse. After grouping the patients according to the type of Acute Lymphoblastic Leukemia, patients with T-ALL presented longer telomere lenght than patients with B-ALL ( 2.4 ± 1.08 Kb versus 1.90 ± 1.67 Kb respectively). High-risk group patients had shorter telomere lengths compared to the intermediate-risk counterpart (1.43 ± 1.54 Kb and 2.29. ± 1.47 Kb respectively). Finally, comparing the telomeres length based on the karyotype analysis, individuals with 46 chromosomes had median telomere length of 1.61 ± 1.4 Kb, which is shorter than those with a karyotype with > 46 chromosomes. In conclusion, the large reduction in the telomere length of lymphoblasts due to their uncontrolled proliferation may be reversible. Telomeres length measurement could provide an important correlation with disease progression and be a useful biomarker of ALL.

Language

Greek

Subject

Cell aging

Telomere end

Κυτταρική γήρανση

Τελομερικά άκρα

Issue date

2022-03-30

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses