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Terapia dirigida de la leucemia linfocítica crónica con venetoclax : Trabajo de Fin de Grado : el efecto de la inhibición de Bcl-2 en el estado redox de las células
Vaz Rivera, Ana
Chronic lymphocytic leukaemia or CLL is a lymphoproliferative disorder and the most common form of leukaemia in the West. The disease is a malignancy of mature CD5+ B lymphocytes, which accumulate in ...the blood, bone marrow and lymphoid tissues. This causes cancer cells to saturate the blood, preventing healthy cells from developing and functioning normally. This disease is generated by somatic mutations that are the same mutations that allow cancer to proliferate. LLC remains alive for two main reasons: the first is the inactivation of the cell's apoptotic mechanisms; and the second is the high amount of pro-survival stimuli that are picked up by the receptors of these malignant B lymphocytes. Receiving and processing these stimuli activates signalling pathways that antagonise apoptosis and promote cancer development and survival. The anti-apoptotic mechanism of interest in this study is the Bcl-2 gene. This gene synthesises for the protein of the same name, Bcl-2, which interacts with the proapoptotic Bax/Bak complex and does not allow it to function; thus preventing cell apoptosis. The common approach to treating this cancer is chemoimmunotherapy, a treatment that causes damage to the genome. This chromosome damage, under normal conditions, activates DNA repair mechanisms that induce apoptosis in the damaged cancer cell; but as we know, in CLL, apoptotic mechanisms are inhibited. For this reason, targeted therapies are proposed, in particular, our study focuses on venetoclax, an oral drug that inhibits the anti-apoptotic protein Bcl-2. The Bcl-2 protein is also an antioxidant and reduces intracellular ROS levels. We also want to study whether inhibiting the anti-apoptotic protein also increases intracellular ROS levels. To this end, this study was carried out on three cell lines: one healthy (LCL), and two sister cancer lines (MEC-1 and MEC-2), the second more aggressive than the first. The results of the study show that venetoclax affects the viability of cancer cells, but not the viability of healthy cells. We can also observe that all three cell lines are sensitive to treatment with respect to ROS production, i.e. the levels of these molecules increase in treated cells compared to untreated cells. However, the increase or decrease in ROS levels does not affect cell survival. Finally, it is notable that the concentration of treatment applied to the cells does not influence cell viability or ROS production.
Type of material - undergraduate thesis
; adult, serious
Publication and manufacture - Ljubljana : [A. Vaz Rivera], 2022
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