Studying the Interaction Between Hyperactive PI3K-AKT and NF-κB Pathways in Differentiated Acute Promyelocytic Leukaemia (APL) Cell Lines

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dc.contributor.advisorJambrovics, Károly
dc.contributor.advisordeptDebreceni Egyetem::Általános Orvostudományi Kar::Biokémiai és Molekuláris Biológiai Intézet
dc.contributor.authorZacharia, Ezra
dc.contributor.departmentDE--Általános Orvostudományi Kar
dc.contributor.opponentDemény, Máté Ágoston
dc.contributor.opponentTürk-Mázló, Anett
dc.contributor.opponentdeptDebreceni Egyetem::Általános Orvostudományi Kar::Orvosi Vegytani Intézet
dc.contributor.opponentdeptDebreceni Egyetem::Általános Orvostudományi Kar::Immunológiai Intézet
dc.date.accessioned2023-05-11T09:15:07Z
dc.date.available2023-05-11T09:15:07Z
dc.date.created2023-03-28
dc.description.abstractAcute Promyelocytic Leukaemia (APL) is induced by the blocking of normal myeloid differentiation by the PML-RARA fusion oncoprotein, produced by the balanced translocation t(15;17) (q22;q12-21). All Trans Retinoic Acid (ATRA) treatment can be used as differentiation therapy in patients with APL, resulting in terminal differentiation of promyelocytes to neutrophil granulocytes. This process can be replicated in-vitro by the administration of ATRA to NB4 cells. Also identified as effective treatment for APL is the drug arsenic trioxide (ATO), which displays synergism when combined with ATRA, prolonging further survival of APL patients in a dose-dependent manner. ATO treatment can lead to complete remission in relapsed APL patients, inducing partial differentiation and apoptosis in those cells. This effect may be due to endogenous superoxide production following arsenic exposure by ATO. In the formation of functioning neutrophil granulocytes, thousands of gene up- and down-regulation processes are involved. A complication of ATRA therapy is the so-called ‘differentiation syndrome’ which causes an acute exaggerated inflammatory response. This study considers inhibition of the PI3K-AKT cellular signalling pathway as a target to achieve better results in differentiation therapy. As such, PHT (combined with ATRA and ATO) in increasing concentrations over time resulted in reduced activity of inflammatory (NF-κB) and apoptotic (FOXO3A) pathways, with reduced production of pro-inflammatory cytokines.
dc.description.correctorLB
dc.description.courseáltalános orvos
dc.description.courselangangol
dc.description.degreeegységes, osztatlan
dc.format.extent53
dc.identifier.urihttps://hdl.handle.net/2437/353023
dc.language.isoen
dc.rights.accessHozzáférhető a 2022 decemberi felsőoktatási törvénymódosítás értelmében.
dc.subjectAcute Promyelocytic Leukaemia
dc.subjectATRA
dc.subjectATO
dc.subjectDifferentiation Syndrome
dc.subject.dspaceDEENK Témalista::Kémia::Biokémia
dc.titleStudying the Interaction Between Hyperactive PI3K-AKT and NF-κB Pathways in Differentiated Acute Promyelocytic Leukaemia (APL) Cell Lines
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Theses (Faculty of Medicine)