Telomeres compose the end portions of human chromosomes, and their main function is to protect the genome. In hematological disorders, telomeres are shortened, predisposing to genetic instability that may cause DNA damage and chromosomal rearrangements, inducing a poor clinical outcome. Studies from 2010 to 2019 were compiled and experimental studies using samples of patients diagnosed with hematological malignancies that reported the size of the telomeres were described. Abnormal telomere shortening is described in cancer, but in hematological neoplasms, telomeres are still shortened even after telomerase reactivation. In this study, we compared the sizes of telomeres in leukemias, myelodysplastic syndrome and lymphomas, identifying that the smallest telomeres are present in patients at relapse. In conclusion, the experimental and clinical data analyzed in this review demonstrate that excessive telomere shortening is present in major hematological malignancies and its analysis and measurement is a crucial step in determining patient prognosis, predicting disease risk and assisting in the decision for targeted therapeutic strategies.The word telomere originates from the Greek words τέλος (telos, end, extremity)+μέρος (meros, part), meaning "part of the extremity". The telomeres compose the end portions of chromosomes and consist of many 5'-TTAGGG-3' noncoding repeats (1).During a normal lifespan, telomeres naturally shorten. However, this can become a problem when excessive telomere shortening is observed in stem cells of both pediatric and adult patients. Healthy cells are predisposed to a division limit, also known as Hayflick limit, of 50 to 70 divisions before the cell undergoes senesce or apoptosis due to telomere attrition (2, 3).Short telomeres are associated with genetic instability, which may characterize them as a predisposition factor for hematological malignancies (4, 5). Human Telomeres and their FunctionsHuman telomeres are the end portions of chromosomes, which act primarily in DNA protection and genomic stability, preventing fusions and damage to the genetic material. Telomeres are composed of approximately 1000 to 2000 base pairs or 5-12 kb of non-coding TTAGGG repeats, which interacts with a group of proteins denominated as Shelterin complex (Figure 1) (3,(6)(7)(8).A major characteristic of telomeres is their progressive shortening that happens naturally with each division of somatic cells. The shortening occurs due to the DNA end replication problem, which consists of the inability of the cellular machinery to effectively synthesize the chromosomes ends during replication, alongside with the lack or insufficiency of pathways that promote telomere elongation, such as telomerase activity or the alternative lengthening of telomeres (ALT) (9-11).Telomere elongation occurs primarily by human telomerase (hTERT) activity, which is a ribonucleoprotein enzyme specialized in neutralizing telomeric DNA attrition by synthesizing new TTAGGG repeats at chromosome ends. This enzyme is composed by two subunits...
Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene (hTERT) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients (N = 244) was statistically significant (p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant (p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant (p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient’s clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.
Glioblastoma multiforme (GBM) is a very aggressive and heterogeneous glioma. Currently, GBM is treated with a combination of surgery, radiotherapy, chemotherapy (e.g. temozolamide) and Tumour Treating Fields. Unfortunately, the mean survival is still around 15 months. This poor prognosis is associated with therapy resistance, tumor recurrence, and limited delivery of drugs due to the blood-brain barrier nature. Nanomedicine, the application of nanotechnology to medicine, has revolutionized many health fields, specifically cancer diagnosis and treatment. This review explores the particularities of different nanosystems (i.e., superparamagnetic, polymeric and gold nanoparticles, and liposomes) as well as how they can be applied to the treatment and diagnosis of GBM. As described, the most of the cited examples are on the preclinical phase; however, positive results were obtained and thus, the distance to achieve an effective treatment is shorter every day.
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