DSpace logo

Use este identificador para citar ou linkar para este item: http://repositorioinstitucional.uea.edu.br//handle/riuea/5344
Registro completo de metadados
Campo DCValorIdioma
dc.contributor.authorAlves, Emanuela Vitória Barbosa-
dc.date.available2023-11-08-
dc.date.available2023-11-21T13:07:03Z-
dc.date.issued2023-07-26-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/5344-
dc.description.abstractEssential thrombocythemia (ET) is characterized by clonal proliferation of megakaryocytes in the bone marrow, which results in an increase in the number of circulating platelets. ET has a higher prevalence in females between the ages of 50 and 60 years. Microvesicles (MVs) are a heterogeneous group of vesicles, originating in the plasma membrane of normal or neoplastic cells, their content and function depend on the cell of origin, their structure is formed by a lipid bilayer and inside there are lipids, proteins, mRNA and miRNA. Studies indicate that MVs participate in fundamental processes in the multiplication and formation of the microenvironment of neoplastic cells and play an important role in the development of cancer in the body. The aim of this study is to characterize the profile of circulating microvesicles in patients diagnosed with Essential Thrombocythemia treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. We will evaluate the medical records of patients to collect sociodemographic and clinical characteristics, perform laboratory tests for hematological analysis, biochemical analysis, and hemostasis tests. To determine the cellular origin of the MVs, the flow cytometry technique will be used with specific antibodies: progenitor cells (CD34), myeloid cells (CD13, CD33 and CD117), leukocytes (CD45), dendritic cells (CD11c), monocytes (CD14) , neutrophils (CD16 and CD66b), T lymphocytes (CD3), B lymphocytes (CD19), NK cells (CD56), platelets (CD41a), erythrocytes (CD235a) and endothelial cells (CD51/61). The group of patients with ET on hydroxyurea treatment had a high level of total circulating microvesicles and populations of MVs CD34, CD13, CD11c, CD14, CD16, CD66b, CD3, CD19, CD56 and CD235a. The high level of these MVs demonstrates that different populations of MVs may be involved in the pathogenesis of ET. Hydroxyurea treatment seems to play a crucial role in decreasing MVs, the present study found an association between the decrease in the number of circulating MVs with increasing treatment time.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectTrombocitemia essencialpt_BR
dc.subjectMicrovesículapt_BR
dc.subjectNeoplasia mieloproliferativapt_BR
dc.subjectEssential thrombocythemiapt_BR
dc.subjectMyeloproliferative neoplasmpt_BR
dc.titleCaracterização do perfil de microvesículas circulantes em pacientes com trombocitemia essencialpt_BR
dc.title.alternativeCharacterization of the profile of circulating microvesicles in patients with essential thrombocythemiapt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2023-11-21T13:07:03Z-
dc.contributor.advisor-co1Mourão, Lucivana Prata de Souza-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.advisor1Tarragô, Andréa Monteiro-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/4644326589690231pt_BR
dc.contributor.referee1Tarragô, Andréa Monteiro-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/4644326589690231pt_BR
dc.contributor.referee2Pontes, Letícia Gomes de-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/8116355457327399pt_BR
dc.contributor.referee3Araújo, Nilberto Dias de-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/2649009048520935pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/7904602249343854pt_BR
dc.description.resumoA Trombocitemia Essencial (TE) é caracterizada pela proliferação desordenada megacariócitos na medula óssea, o que resulta em um aumento no número de plaquetas circulantes. A TE tem uma prevalência maior no sexo feminino entre a idade de 50 a 60 anos. As microvesículas (MVs) são um grupo heterogêneo de vesículas, originados na membrana plasmáticas das células saudáveis ou neoplásicas, o conteúdo e função depende da célula de origem, possui uma estrutura formada por uma bicamada lipídica e em seu interior existem lipídios, proteínas, mRNA e miRNA. Estudos indicam que as MVs participam de processos fundamentais na multiplicação e na formação do microambiente das células neoplásicas e possuem um importante papel no desenvolvimento do câncer no organismo. O objetivo deste estudo foi caracterizar o perfil das microvesículas circulantes em pacientes com diagnostico de Trombocitemia Essencial atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Os prontuários dos pacientes foram avaliados para coleta das características sociodemográficas e clínicas, realizamos exames laboratoriais para análises hematológicas, análises bioquímicas e testes da hemostasia. Para determinar a origem celular das MVs utilizamos a técnica de citometria de fluxo com anticorpos específicos: células progenitoras (CD34), células mieloides (CD13, CD33 e CD117), leucócitos (CD45), células dendríticas (CD11c), monócitos (CD14), neutrófilos (CD16 e CD66b), linfócitos T (CD3), linfócitos B (CD19), células NK (CD56), plaquetas (CD41a), eritrócitos (CD235a) e células endoteliais (CD51/61). O grupo de pacientes com TE em tratamento com hidroxiureia possuíam um nível elevado de microvesículas circulantes totais e das populações de MVs CD34, CD13, CD33, CD11c, CD14, CD16, CD66b, CD3, CD19, CD56 e CD235a. O nível elevado dessas MVs demostra que diversas populações de MVs podem estar envolvidas na patogênese da TE. O tratamento com hidroxiureia parece desempenhar um papel crucial na diminuição das MVs, o presente estudo encontrou uma associação entre a diminuição do número de MVs circulantes com o aumento do tempo de tratamento.pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
dc.relation.references1. Ji, S. et al. Phagocytosis by endothelial cells inhibits procoagulant activity of platelets of essential thrombocythemia in vitro. Journal of Thrombosis and Haemostasis 18, 222–233 (2020). 2. Hoffbrand, A. V, Higgs, D. R., Keeling, D. M. & Mehta, A. B. Postgraduate Haematology. (Wiley-Blackwell, 2016). 3. Ferrer-Marín, F., Cuenca-Zamora, E. J., Guijarro-Carrillo, P. J. & Teruel-Montoya, R. Emerging role of neutrophils in the thrombosis of chronic myeloproliferative neoplasms. International Journal of Molecular Sciences vol. 22 1–14 Preprint at https://doi.org/10.3390/ijms22031143 (2021). 4. Longhitano, L. et al. The role of inflammation and inflammasome in myeloproliferative disease. Journal of Clinical Medicine vol. 9 1–11 Preprint at https://doi.org/10.3390/jcm9082334 (2020). 5. Ståhl, A. lie, Johansson, K., Mossberg, M., Kahn, R. & Karpman, D. Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases. Pediatric Nephrology vol. 34 11–30 Preprint at https://doi.org/10.1007/s00467-017-3816-z (2019). 6. Yates, A. G. et al. In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part I: Health and Normal Physiology. Journal of Extracellular Vesicles vol. 11 Preprint at https://doi.org/10.1002/jev2.12151 (2022). 7. Clancy, J. W., Schmidtmann, M. & D’Souza-Schorey, C. The ins and outs of microvesicles. FASEB BioAdvances vol. 3 399–406 Preprint at https://doi.org/10.1096/fba.2020-00127 (2021). 8. Lv, Y. M., Tan, J., Miao, Y. & Zhang, Q. The role of microvesicles and its active molecules in regulating cellular biology. Journal of Cellular and Molecular Medicine vol. 23 7894–7904 Preprint at https://doi.org/10.1111/jcmm.14667 (2019). 9. Barteneva, N. S. et al. Circulating microparticles: square the circle. BMC Cell Biol 14, (2013). 10. Forte, D., Barone, M., Palandri, F. & Catani, L. The “vesicular intelligence” strategy of blood cancers. Genes vol. 12 Preprint at https://doi.org/10.3390/genes12030416 (2021). 11. Rackov, G. et al. Vesicle-mediated control of cell function: The role of extracellular matrix and microenvironment. Frontiers in Physiology vol. 9 Preprint at https://doi.org/10.3389/fphys.2018.00651 (2018). 12. Barbui, T., Finazzi, G. & Falanga, A. Myeloproliferative neoplasms and thrombosis. Blood vol. 122 2176–2184 Preprint at https://doi.org/10.1182/blood-2013-03-460154 (2013). 13. Pagliarini-e-Silva, S. et al. Evaluation of the association between the JAK2 46/1 haplotype and chronic myeloproliferative neoplasms in a Brazilian population. Clinics 68, 5–9 (2013). 14. Porto-Soares, M. A. et al. Clinical and molecular profile of a Brazilian cohort of patients with classical BCR-ABL1-negative myeloproliferative neoplasms. Hematol Transfus Cell Ther 42, 238–244 (2020). 15. Lima, J. G., Rauber, L. & Lopes, T. B. Perfil dos pacientes com neoplasia mieloproliferativa cromossomo philadelfia negativo na unidade de alta complexidade oncológica do Hospital São José em Criciúma/SC no período de 2008 a 2015. Arquivos Catarinenses de Medicina 47, 2–12 (2018). 57 16. Mehta, J., Wang, H., Iqbal, S. U. & Mesa, R. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma 55, 595–600 (2014). 17. Khoury, J. D. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia vol. 36 1703–1719 Preprint at https://doi.org/10.1038/s41375-022-01613-1 (2022). 18. Agarwal, M. B. et al. Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Indian Journal of Medical and Paediatric Oncology 36, 3–16 (2015). 19. Santoro, C. et al. Role of treatment on the development of secondary malignancies in patients with essential thrombocythemia. Cancer Med 6, 1233–1239 (2017). 20. Awada, H., Voso, M. T., Guglielmelli, P. & Gurnari, C. Essential thrombocythemia and acquired von willebrand syndrome: The shadowlands between thrombosis and bleeding. Cancers vol. 12 1–19 Preprint at https://doi.org/10.3390/cancers12071746 (2020). 21. Farina, M., Russo, D. & Hoffman, R. The possible role of mutated endothelial cells in myeloproliferative neoplasms. Haematologica vol. 106 2813–2823 Preprint at https://doi.org/10.3324/haematol.2021.278499 (2021). 22. Puga, M. L. et al. Performance of microvesicles as biomarkers of clinical outcome in sepsis and trauma: A pilot study. Biomedicine and Pharmacotherapy 146, (2022). 23. Falanga, A., Tartari, C. J. & Marchetti, M. Microparticles in tumor progression. in Thrombosis Research vol. 129 (2012). 24. Trappenburg, M. C. et al. Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia. Haematologica 94, 911–918 (2009). 25. Kissova, J., Ovesna, P., Bulikova, A., Zavřelova, J. & Penka, M. Increasing procoagulant activity of circulating microparticles in patients with Philadelphia-negative myeloproliferative neoplasms: A single-centre experience. Blood Coagulation and Fibrinolysis 26, 448–453 (2015). 26. Zhang, W. et al. Clinical significance of circulating microparticles in Ph- myeloproliferative neoplasms. Oncol Lett 14, 2531–2536 (2017). 27. Aswad, M. H. et al. High Level of Circulating Microparticles in Patients with BCR/ABL Negative Myeloproliferative Neoplasm - a Pilot Study. Klin. Onkol 32, 109–116 (2019). 28. Aswad, M. H., Kissova, J., Ovesna, P., Rihova, L. & Penka, M. The clinical significance of circulating microparticles concerning thrombosis in BCR/ABL1-negative myeloproliferative neoplasms. In Vivo (Brooklyn) 35, 3345–3353 (2021). 29. Demchenko, A. P. Beyond annexin V: Fluorescence response of cellular membranes to apoptosis. Cytotechnology vol. 65 157–172 Preprint at https://doi.org/10.1007/s10616-012-9481-y (2013). 30. Voukalis, C., Shantsila, E. & Lip, G. Y. H. Microparticles and cardiovascular diseases. Annals of Medicine vol. 51 193–223 Preprint at https://doi.org/10.1080/07853890.2019.1609076 (2019). 31. Aharon, A., Rebibo-Sabbah, A., Tzoran, I. & Levin, C. Extracellular Vesicles in Hematological Disorders. Rambam Maimonides Med J 5, e0032 (2014). 32. Marchetti, M. et al. Phospholipid-dependent procoagulant activity is highly expressed by circulating microparticles in patients with essential thrombocythemia. Am J Hematol 89, 68–73 (2014). 58 33. Charpentier, A. et al. Microparticle phenotypes are associated with driver mutations and distinct thrombotic risks in essential thrombocythemia. Haematologica vol. 101 e365–e368 Preprint at https://doi.org/10.3324/haematol.2016.144279 (2016). 34. Taniguchi, Y. et al. Elevated plasma levels of procoagulant microparticles are a novel risk factor for thrombosis in patients with myeloproliferative neoplasms. Int J Hematol 106, 691–703 (2017). 35. Moliterno, A. R., Williams, D. M., Rogers, O., Isaacs, M. A. & Spivak, J. L. Phenotypic variability within the JAK2 V617F-positive MPD: Roles of progenitor cell and neutrophil allele burdens. Exp Hematol 36, 1480-1486.e2 (2008). 36. Zhang, J. et al. Selective surface marker and miRNA profiles of CD34+ blast-derived microvesicles in chronic myelogenous leukemia. Oncol Lett 14, 1866–1874 (2017). 37. Sukriti, S. et al. Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis. Aliment Pharmacol Ther 47, 1151–1161 (2018). 38. Connor, D. E., Ma, D. D. F. & Joseph, J. E. Flow cytometry demonstrates differences in platelet reactivity and microparticle formation in subjects with thrombocytopenia or thrombocytosis due to primary haematological disorders. Thromb Res 132, 572–577 (2013). 39. Weisel, J. W. & Litvinov, R. I. Red blood cells: the forgotten player in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis vol. 17 271–282 Preprint at https://doi.org/10.1111/jth.14360 (2019). 40. Van Beers, E. J. et al. Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease. Haematologica 94, 1513–1519 (2009). 41. Rubin, O. et al. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation. Transfusion (Paris) 53, 1744–1754 (2013). 42. Carobbio, A. et al. Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: A systematic review and meta-analysis. Blood Advances vol. 3 1729–1737 Preprint at https://doi.org/10.1182/bloodadvances.2019000211 (2019). 43. Piccin, A. et al. Observational retrospective study of vascular modulator changes during treatment in essential thrombocythemia. Translational Research 184, 21–34 (2017). 44. Barone, M. et al. A specific host/microbial signature of plasma-derived extracellular vesicles is associated to thrombosis and marrow fibrosis in polycythemia vera. Cancers (Basel) 13, (2021). 45. Jung, K. H. et al. Circulating endothelial microparticles as a marker of cerebrovascular disease. Ann Neurol 66, 191–199 (2009). 46. Lackner, P. et al. Cellular microparticles as a marker for cerebral vasospasm in spontaneous subarachnoid hemorrhage. Stroke 41, 2353–2357 (2010). 47. Torres, D. G. et al. JAK2 Variant Signaling: Genetic, Hematologic and Immune Implication in Chronic Myeloproliferative Neoplasms. Biomolecules vol. 12 Preprint at https://doi.org/10.3390/biom12020291 (2022). 48. Hekimoğlu, H., Toprak, S. F. & Sözer, S. JAK2V617F-Positive Endothelial Cells Induce Apoptosis and Release JAK2V617F-Positive Microparticles. Turkish Journal of Hematology 39, 13–21 (2022). 49. Prestipino, A. et al. Oncogenic JAK2 V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci. Transl. Med vol. 10 http://stm.sciencemag.org/ (2018). 59 50. Dingli, D. & Tefferi, A. Hydroxyurea: The Drug of Choice for Polycythemia Vera and Essential Thrombocythemia. Myeloproliferative Disease 1, 69–74 (2006). 51. Besses, C. et al. Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients. Br J Haematol 152, 413–419 (2011). 52. Falanga, A., Marchetti, M., Vignoli, A., Balducci, D. & Barbui, T. Leukocyte-platelet interaction in patients withessential thrombocythemia and polycythemia vera. Exp Hematol 33, 523–530 (2005). 53. Falanga, A. et al. V617F JAK-2 mutation in patients with essential thrombocythemia: relation to platelet, granulocyte, and plasma hemostatic and inflammatory molecules. Exp Hematol 35, 702–711 (2007). 54. Eitan, E. et al. Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes. Sci Rep 7, (2017).pt_BR
dc.publisher.initialsUEApt_BR
Aparece nas coleções:DISSERTAÇÃO - PPCAH Programa de Pós-Graduação em Ciências Aplicadas à Hematologia

Arquivos associados a este item:
Arquivo Descrição TamanhoFormato 
Caracterização do perfil de microvesículas circulantes em pacientes com trombocitemia essencial.pdf5,26 MBAdobe PDFVisualizar/Abrir
Mostrar registro simples do item Visualizar estatísticas


Os itens no repositório estão protegidos por copyright, com todos os direitos reservados, salvo quando é indicado o contrário.