Extracelluláris vesiculák minden szervezetben képződnek. Három legintenzívebben vizsgált csoportjuk az apoptotikus testek, a microvesiculák és az exosomák. A sejtek közötti kommunikációban, immunreakciókban, angiogenezisben betöltött szerepük csak néhány az eddig megismertek közül. A fiziológiás folyamatok mellett sokféle betegségben leírták változásaikat; a patomechanizmusban betöltött szerepük mellett felvetődik potenciális használatuk biomarkerekként. A szerzők betekintést kívánnak nyújtani az extracelluláris vesiculák kutatásába, kiemelve azt a néhány tanulmányt, amely a hematológiai malignitásokra fókuszált. A microvesiculák és exosomák vérplazmában mért mennyisége, a terápia során megfigyelt minőségi változása miatt felmerült, hogy a diagnosztikában, prognosztikában, illetve a minimális residualis betegség monitorozásában is használhatók lehetnek. Akut myeloid leukaemiában a természetes ölősejtek aktivitásának szupresszálásában bizonyított a blasteredetű exosomák szerepe. Krónikus lymphoid leukaemiában a microvesiculák közreműködése valószínű a gyógyszer-rezisztencia kialakulásában is. Orv. Hetil., 2016, 157(35), 1379–1384.
György, B., Szabó, T. G., Pásztói, M., et al.: Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell. Mol. Life Sci., 2011, 68(16), 2667–2688.
Harding, C., Heuser, J., Stahl, P.: Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur. J. Cell Biol., 1984, 35(2), 256–263.
Pan, B. T., Johnstone, R. M.: Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell, 1983, 33(3), 967–978.
Raposo, G., Nijman, H. W., Stoorvogel, W., et al.: B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med., 1996, 183(3), 1161–1172.
Théry, C., Ostrowski, M., Segura, E.: Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol., 2009, 9(8), 581–593.
Kalra, H., Simpson, R. J., Ji, H., et al.: Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol., 2012, 10(12), e1001450.
Johnstone, R. M., Adam, M., Hammond, J. R., et al.: Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem., 1987, 262(19), 9412–9420.
Hristov, M., Erl, W., Linder, S., et al.: Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood, 2004, 104(9), 2761–2766.
Bergsmedh, A., Szeles, A., Henriksson, M., et al.: Horizontal transfer of oncogenes by uptake of apoptotic bodies. Proc. Nat. Acad. Sci. U.S.A., 2001, 98(11), 6407–6411.
Van Engeland, M., Nieland, L. J., Ramaekers, F. C., et al.: Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry, 1998, 31(1), 1–9.
Yuana, Y., Sturk, A., Nieuwland, R.: Extracellular vesicles in physiological and pathological conditions. Blood Rev., 2013, 27(1), 31–39.
Böing, A. N., Hau, C. M., Sturk, A., et al.: Platelet microparticles contain active caspase 3. Platelets, 2008, 19(2), 96–103.
Valadi, H., Ekström, K., Bossios, A., et al.: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9(6), 654–659.
Akers, J. C., Gonda, D., Kim, R., et al.: Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol., 2013, 113(1), 1–11.
Van der Pol, E., Böing, A. N., Harrison, P., et al.: Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev., 2012, 64(3), 676–705.
Esquela-Kerscher, A., Slack, F. J.: Oncomirs – microRNAs with a role in cancer. Nat. Rev. Cancer, 2006, 6(4), 259–269.
Hannafon, B. N., Ding, W. Q.: Intercellular communication by exosome-derived microRNAs in cancer. Int. J. Mol. Sci., 2013, 14(7), 14240–14269.
Szczepanski, M. J., Szajnik, M., Welsh, A., et al.: Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica, 2011, 96(9), 1302–1309.
Clayton, A., Court, J., Navabi, H., et al.: Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. J. Immunol. Methods, 2001, 247(1–2), 163–174.
Huan, J., Hornick, N. I., Shurtleff, M. J., et al.: RNA trafficking by acute myelogenous leukemia exosomes. Cancer Res., 2013, 73(2), 918–929.
Wojtuszkiewicz, A., Schuurhuis, G. J., Kessler, F. L., et al.: Exosomes secreted by apoptosis-resistant acute myeloid leukemia (AML) blasts harbor regulatory network proteins potentially involved in antagonism of apoptosis. Mol. Cell. Proteomics, 2016, 15(4), 1281–1298.
Dragovic, R. A., Gardiner, C., Brooks, A. S., et al.: Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine, 2011, 7(6), 780–788.
Tissot, J. D., Canellini, G., Rubin, O., et al.: Blood microvesicles: From proteomics to physiology. Translat. Proteomics, 2013, 1(1), 38–52.
Taylor, D. D., Gercel-Taylor, C.: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol., 2008, 110(1), 13–21.
Rabinowits, G., Gerçel-Taylor, C., Day, J. M., et al.: Exosomal microRNA: a diagnostic marker for lung cancer. Clin. Lung Cancer, 2009, 10(1), 42–46.
Hong, C. S., Muller, L., Boyiadzis, M., et al.: Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. PLoS ONE, 2014, 9(8), e103310.
Aharon, A., Rebibo-Sabbah, A., Tzoran, I., et al.: Extracellular vesicles in hematological disorders. Rambam Maimonides Med. J., 2014, 5(4), e0032.
Szczepanski, M. J., Szajnik, M., Welsh, A., et al.: Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors. Cancer Immunol. Immunother., 2010, 59(1), 73–79.
Caivano, A., Laurenzana, I., De Luca, L., et al.: High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. Tumour Biol., 2015, 36(12), 9739–9752.
Ghosh, A. K., Secreto, C. R., Knox, T. R., et al.: Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression. Blood, 2010, 115(9), 1755–1764.
Bergmann, C., Strauss, L., Wieckowski, E., et al.: Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression. Head Neck, 2009, 31(3), 371–380.
Valenti, R., Huber, V., Iero, M., et al.: Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res., 2007, 67(7), 2912–2915.
Bacher, U., Schnittger, S., Haferlach, T.: Molecular genetics in acute myeloid leukemia. Curr. Opin. Oncol., 2010, 22(6), 646–655.
Chapuis, N., Tamburini, J., Cornillet-Lefebvre, P., et al.: Autocrine IGF-1/IGF-1R signaling is responsible for constitutive PI3K/Akt activation in acute myeloid leukemia: therapeutic value of neutralizing anti-IGF-1R antibody. Haematologica, 2010, 95(3), 415–423.
Olsnes, A. M., Hatfield, K. J., Bruserud, Ø.: The chemokine system and its contribution to leukemogenesis and treatment responsiveness in patients with acute myeloid leukemia. J. Balkan Union Oncol., 2009, 14(Suppl. 1), S131–S140.
Hornick, N. I., Huan, J., Doron, B., et al.: Serum exosome microRNA as a minimally-invasive early biomarker of AML. Sci. Rep., 2015, 5, 11295.
Hong, C. S., Muller, L., Whiteside, T. L., et al.: Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Front. Immunol., 2014, 5, 160.