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Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

ABSTRACT: 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.

SUBMITTER: Nogueira BMD

PROVIDER: S-EPMC8535500 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

Nogueira Beatriz Maria Dias BMD da Costa Pantoja Laudreísa L da Silva Emerson Lucena EL Mello Júnior Fernando Augusto Rodrigues FAR Teixeira Eliel Barbosa EB Wanderley Alayde Vieira AV da Silva Maués Jersey Heitor JH de Moraes Filho Manoel Odorico MO de Moraes Maria Elisabete Amaral MEA Montenegro Raquel Carvalho RC Khayat André Salim AS Moreira-Nunes Caroline Aquino CA

Genes 20211017 10

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 ...[more]

PMID: 34681025

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Project description:BackgroundIn our recent study, Periostin was up-regulated in prostate cancer(PCa) compared with benign prostate hyperplasia (BPH) by proteomics analysis of prostate biopsies. We investigated the effect of sliencing Periostin by RNA interference (RNAi) on the proliferation and migration of PCa LNCap cell line.MethodsAll the prostate biopsies from PCa, BPH and BPH with local prostatic intraepithelial neoplasm(PIN) were analyzed by iTRAQ(Isobaric tags for relative and absolute quantification) technology. Western blotting and immunohistochemical staining were used to verify Periostin expression in the tissues of PCa. Periostin expression in different PCa cell lines was determined by immunofluorescence staining, western blotting and reverse transcription PCR(RT-PCR). The LNCap cells with Periostin expression were used for transfecting shRNA-Periostin lentiviral particles. The efficancy of transfecting shRNA lentiviral particles was evaluated by immunofluorescence, western blotting and Real-time PCR. The effect of silencing Periostin expression by RNAi on proliferation of LNCap cells was determined by MTT assay and tumor xenografts. The tissue slices from theses xenografts were analyzed by hematoxylin and eosin(HE) staining. The expression of Periostin in the xenografts was deteminned by Immunohistochemical staining and western blotting. The migration of LNCap cells after silencing Periostin gene expression were analyzed in vitro.ResultsPeriostin as the protein of interest was shown 9.12 fold up-regulation in PCa compared with BPH. The overexpression of Periostin in the stroma of PCa was confirmed by western blotting and immunohistochemical staining. Periostin was only expressed in PCa LNCap cell line. Our results indicated that the transfection ratio was more than 90%. As was expected, both the protein level and mRNA level of Periostin in the stably expressing shRNA-Periostin LNCap cells were significantly reduced. The stably expressing shRNA-Periostin LNCap cells growed slowly in vitro and in vivo. The tissues of xenografts as PCa were verificated by HE staining. Additionally, the weak positive Periostin expressed tumor cells could be seen in the tissues of 6 xenografts from the group of down-regulated Periostin LNCap cells which had a significant decrease of the amount of Periostin compared to the other two group. Furthermore, our results demonstrated that sliencing Periostin could inhibit migration of LNCap cells in vitro.ConclusionsOur data indicates that Periostin as an up-regulated protein in PCa may be a promising target of therapeutical intervention for PCa in future.

Dataset Information

Telomerase (hTERT) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

Publications

Telomerase (<i>hTERT</i>) Overexpression Reveals a Promising Prognostic Biomarker and Therapeutical Target in Different Clinical Subtypes of Pediatric Acute Lymphoblastic Leukaemia.

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