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The role of exosomes in chronic myeloid leukemia
Březinová, Lenka ; Krijt, Matyáš (advisor) ; Holada, Karel (referee)
Exosomes are extracellular vesicles of a size range 30-150 nm whose function has been explored in chronic myeloid leukemia (CML) due to their role in proliferation of CML cells, remodelling the bone marrow niche, angiogenesis and resistance to treatment with tyrosin- kinase inhibitors (TKIs). Although BCR-ABL kinase is effectively targeted by TKIs, 20-30 % of patients remain resistant to treatment. Resistance of CML cells to TKIs treatment is supported by exosomes. Exosomes transport proteins, nucleic acids, chemokines and small molecules that stimulate anti-apoptotic or suppress pro-apoptotic processes in leukemic cells. Anti-apoptotic processes are especially enhanced by upregulated protein levels: TGF- β1, USP6 and FGF2 and various types of RNA: miR-365, miR-21, Hsa_circ_0058493 and mRNA for BCR-ABL. In contrast leukemic cells tend to reduce the number of pro-apoptotic molecules, including miR-320, miR-328 and miR-146a-5p. Leukemic cells modify the bone marrow microenvironment through exosomes in the way to support their survival and also in order to adjust expression of adhesion and pro- angiogenic molecules. An important role in those processes play miR-126, miR-210 and miR- 92a. Neither the number of processes affected by CML exosomes nor their potential use in the treatment of CML is...
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