Search

Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL. There are approximately one thousand miRNAs in the human genome. They are expressed in specific tissues and changes in this expression are associated with different pathologies. In recent years, several studies have focused on the role of regulatory miRNAs in the pathogenesis of various diseases, including CLL. It has become evident that the profiles of miRNAs have great potential for application in the evaluation of CLL prognosis, since changes in miRNA expression profiles contribute to cell survival, proliferation and development of the disease. The deletion 13q14, the most prevalent alteration in CLL, leads to the deletion of the human tumor suppressor genes miR-15a and miR-16-1, which act on cell proliferation and in the process of apoptosis. Therefore, in patients with 13q deletion, loss of miR-15a and miR-16-1 displaces the expression balance for higher levels of Bcl-2 anti-apoptotic and pro-apoptotic p53 proteins. Regarding these microRNAs, the correlation of miR-15a and miR-16-1 with low-risk CLL is of particular interest. In this context, this mini review summarizes the current evidences on the role of regulatory miRNAs in the pathogenesis of CLL, particularly miR-15a and miR-16-1, involved on cell proliferation and apoptosis. In addition, it is our intention to highlight the potential role of micro RNAs as a marker of prognosis in this disease and to arouse interest in future studies addressing this interesting issue. Several current and future studies may shed light on the role of microRNAs in the pathogenesis of CLL, possibly leading to the development of new laboratory biomarkers., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective/background: From clinical and biological points of view, chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by a progressive accumulation of lymphocytes in the peripheral blood, bone marrow, and lymphoid organs. New prognostic markers in CLL may be useful to clinicians for predicting outcome and in clinical decision-making. The aim of this study was to evaluate the potential prognostic value of the apoptotic/survival-controlling proteins and protein tyrosine kinase ZAP-70 gene expression in CLL patients and control individuals, correlating such findings with patients' clinical data., Methods: Fifty-three patients diagnosed with CLL attending the hematology service of a clinical hospital, and 24 healthy individuals with no history of leukemia (Control group) were enrolled in this study. Analyses of apoptotic/survival-controlling proteins were performed by western blot and ZAP-70 gene expression was evaluated by real-time polymerase chain reaction., Results: Significant differences were observed for the p-p38, Mcl-1 long, and Mcl-1 short proteins when patients were compared with CLL and controls. A positive correlation between the results for Mcl-1 short and Mcl-1 long and lymphocyte count was observed, corroborating the hypothesis of an imbalance between proteins of cell survival pathways/apoptosis in CLL., Conclusion: ZAP-70 gene expression was not detected as a discriminant biomarker in these CLL patients. An imbalance between apoptosis-related proteins was observed in the present study, corroborating the hypothesis of increased survival of lymphocytes in CLL patients., (Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.)