DSpace logo

Please use this identifier to cite or link to this item: http://repositorioinstitucional.uea.edu.br//handle/riuea/4079
Full metadata record
DC FieldValueLanguage
dc.contributor.authorTorres, Dania Isamary Gutierrez-
dc.date.available2022-07-29-
dc.date.available2022-08-10T16:07:44Z-
dc.date.issued2022-05-20-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4079-
dc.description.abstractBCR/ABL1 negative chronic myeloproliferative neoplasms are clonal diseases caused by aberrant proliferation of hematopoietic cells in the bone marrow and excessive accumulation of mature blood elements in peripheral blood. Polycythemia vera, essential thrombocythemia and primary myelofibrosis are the most classic entities within this classification of hematological diseases, which have in common genetic rearrangements in one of the main intracellular signaling pathways: the JAK2/STAT5 pathway. The JAK2 gene encodes the Janus kinase 2 (JAK2) protein, involved in cell proliferation and differentiation processes. JAK2V617F is the most frequent and most studied variant in this group of diseases due to its ability to generate several clinical phenotypes. Variants on exon 12 of the JAK2 gene are screened in JAK2V617F negative individuals, comprising approximately 3% of cases. Although JAK2V617F and JAK2 exon 12 variants are the main research targets in BCR/ABL1 negative Chronic Myeloproliferative Neoplasms, new variants throughout the gene have been identified. Objective: The study aimed to molecularly characterize variants in the JAK2 gene in patients with BCR/ABL1 negative Chronic Myeloproliferative Neoplasms: Polycythemia vera, Essential Thrombocythemia and Myelofibrosis. Methodology: We evaluated 75 patients diagnosed with BCR/ABL1 negative myeloproliferative neoplasms: Polycythemia vera, Essential Thrombocythemia and Myelofibrosis. Clinical data were obtained from medical records. Laboratory data were obtained from sample collections during the follow-up of subjects. Molecular evaluation was performed using conventional Polymerase Chain Reaction and Sanger Sequencing to detect variants in the coding region of the JAK2 gene. Statistical analysis of categorical variables was performed using the Chi-Square test. Kruskal-Wallis and Mann-Whitney tests were used to analyze numerical variables, when convenient. p <0.05 values were considered statistically significant. Results: Sanger sequencing demonstrated the presence of rs907414891, rs2230722, rs2230723, rs10119726, rs576746768, rs77375493 (JAK2V617F), rs2230728, rs2230724, rs41316003 and rs55930140 in the coding region of the JAK2 gene, considering rs77375493 the most frequent variant in individuals with Polycythemia vera. Coexistence of variants was detected in Polycythemia vera and Thrombocythemia, with the combination of variants rs2230722/rs77375493/rs2230724 being the most predominant in both hematological diseases with evidence of alterations in hematological parameters. Conclusions: Individuals with BCR/ABL1 negative chronic myeloproliferative neoplasms with the rs2230724, rs2230722 and rs77375493 variants both separately and together show slight alterations in the clinical-laboratory profile, especially in concomitance with the rs77375493 variant, demonstrating involvement in the instability of regulatory mechanisms at the protein level and possibly the myeloproliferative phenotypept_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectJanus quinasept_BR
dc.subjectNeoplasias Mieloproliferativas crônicaspt_BR
dc.subjectinalização intracelulapt_BR
dc.subjectSequenciamento de Sangerpt_BR
dc.subjectChronic myeloproliferative neoplasmspt_BR
dc.titleCaracterização molecular de variantes no gene JAK2 em pacientes com neoplasias mieloproliferativas crônicas BCR/ABL1 negativopt_BR
dc.title.alternativeMolecular characterization of JAK2 gene variants in patients with BCR/ABL1 negative chronic myeloproliferative neoplasmspt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-10T16:07:44Z-
dc.contributor.advisor-co1Mourão, Lucivana 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.referee1Passos, Leny Nascimento da Motta-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/8194622149198642pt_BR
dc.contributor.referee2Sadahiro, Aya-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/8658798733544812pt_BR
dc.contributor.referee3Torres, Katia Luz-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/5785470863950566pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/9629713669817057pt_BR
dc.description.resumoAs neoplasias mieloproliferativas crônicas BCR/ABL1 negativo são doenças clonais causadas pela proliferação aberrante de células hematopoiéticas na medula óssea e acumulação excessiva de elementos sanguíneos maduros no sangue periférico. Policitemia vera, trombocitemia essencial e mielofibrose primária constituem as entidades mais clássicas dentro desta classificação de doenças hematológicas, as quais têm em comum rearranjos genéticos em uma das principais vias de sinalização intracelular: a via JAK2/STAT5. O gene JAK2 codifica a proteína Janus quinase 2 (JAK2), envolvida em processos de proliferação e diferenciação celular. JAK2V617F é a variante mais frequente e de maior estudo neste grupo de doenças pela habilidade de gerar diversos fenótipos clínicos. Variantes no éxon 12 do gene JAK2 pesquisam-se em indivíduos JAK2V617F negativos, compreendendo aproximadamente 3% dos casos. Embora JAK2V617F e variantes no éxon 12 de JAK2 constituam os principais alvos de pesquisa nas Neoplasias Mieloproliferativas crônicas BCR/ABL1 negativo, novas variantes em toda a extensão do gene têm sido identificadas. Objetivo: O estudo visou caracterizar molecularmente variantes no gene JAK2 em pacientes com Neoplasias Mieloproliferativas Crônicas BCR/ABL1 negativo: Policitemia vera, Trombocitemia Essencial e Mielofibrose. Metodologia: Foram avaliados 75 pacientes com diagnóstico de neoplasias mieloproliferativas BCR/ABL1 negativo: Policitemia vera, Trombocitemia essencial e Mielofibrose. Dados clínicos obtiveram-se de prontuários médicos. Dados laboratoriais obtiveram-se de coletas de amostras durante o seguimento dos indivíduos. Realizou-se avaliação molecular mediante Reação em cadeia de Polimerase convencional e Sequenciamento de Sanger para detecção de variantes na região codificante do gene JAK2. Análise estatística de variáveis categóricas foi realizada pelo teste Qui-Quadrado. Os testes Kruskal-Wallis e Mann-Whitney foram utilizados para análise de variáveis numéricas, quando for conveniente. Valores de p < 0.05 consideraram-se estatisticamente significativos Resultados: Sequenciamento de Sanger demonstrou a presença de rs907414891, rs2230722, rs2230723, rs10119726, rs576746768, rs77375493 (JAK2V617F), rs2230728, rs2230724, rs41316003 e rs55930140 na região codificante do gene JAK2, considerando rs77375493 a variante mais frequente em indivíduos com Policitemia vera. Coexistência de variantes detectou-se na policitemia vera e na trombocitemia, sendo a combinação de variantes rs2230722/ rs77375493 /rs2230724 a mais predominante em ambas doenças hematológicas com evidência de alterações em parâmetros hematológicos. Conclusões: indivíduos com Neoplasias Mieloproliferativas crônicas BCR/ABL1 negativo com as variantes rs2230724, rs2230722 e rs77375493 tanto separada como conjuntamente evidenciam alterações discretas no perfil clínico-laboratorial, especialmente em concomitância com a variante rs77375493, demonstrando envolvimento na instabilidade de mecanismos regulatórios em nível proteico e possivelmente no fenótipo mieloproliferativopt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
dc.relation.references56 7. Bortolheiro, T.C.; Chiattone, C.S. Leucemia mielóide crônica: História natural e classificação. Rev. Bras. Hematol. Hemoter. 2008, 30, 3–7, doi: 10.1590/S1516- 84842008000500003. 8. Rowley, J.D. A story of swapped ends. Science. 2013, 340, 1412–1413, doi: 10.1126/science.1241318. 9. Arber, D.A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M.; Le Beau, M.; Bloomfield, C.; Cazzola, M.; Vardiman, J. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016, 127, 2391–2405, doi: 10.1182/blood-2016-03-643544. 10. Barbui, T.; Thiele, J.; Gisslenger, H.; Kvasnicka, H.M.; Vannucchi, A.; Guglielmelli, P.; Orazi, A.; Tefferi, A. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: Document summary and in-depth discussion. Blood Cancer, J. 2018, 8, 1–11, doi: 10.1038/s41408-018-0054-y. 11. Ortmann, C.A.; Kent, D.G.; Nangalia, J.; Silber, Y.; Wedge, D.C.; Grinfeld, J.; Baxter, E.J.; Massie, C.E.; Papaemmanuil, E.; Menon, S.; Godfrey, A.L.; Dimitropoulou, D.; Guglielmelli, P.; Bellosillo, B.; Besses, C.; Döhner , K.; Harrison, C.N.; Vassiliou, G.S.; Vannucchi, A.; Campbell, P.J.; Green, A.R. Effect of mutation order on myeloproliferative neoplasms. N. Engl. J. Med. 2015, 372, 601–612, doi: 10.1056/NEJMoa1412098. 12. Campbell, P.J.; Green, A.R. The myeloproliferative disorders. N. Engl. J. Med. 2006, 57, 428–435, doi: 10.1177/003693306501000606. 13. Grinfeld, J.; Nangalia, J.; Baxter, E.J.; Wedge, D.C.; Angelopoulos, N.; Cantrill, J.; Godfrey, A.L.; Papaemmanuil, E.; Gundem, G.; MacLean, C.; Cook, J.; O’Neil, L.; O’Meara, S.; Teague, J.W.; Butler, A.P.; Massie, C.E.; Williams, N.; Nice, F.L.; Andersen, C.L.; Hasselbalch, H.C.; Guglielmelli, P.; Mullin, M.F.; Vannucchi, A.M.; Harrison, C.N.; Gerstung, M.; Green, A.R.; Campbell, P.J. Classification and Personalized Prognosis in Myeloproliferative Neoplasms. N. Engl. J. Med. 2018, 379, 1416–1430, doi: 10.1056/NEJMoa1716614. 14. Szuber, N.; Vallapureddy, R.; Penna, D.; Lasho, T.L.; Finke, C.; Hanson, C.A.; Ketterling, R.P.; Pardanni, A.; Gangat, N.; Tefferi, A. Myeloproliferative neoplasms in the young: Mayo Clinic experience with 361 patients age 40 years or younger. Am. J. Hematol. 2018, 93, 1474–1484, doi: 10.1002/ajh.25270. 15. Harrison, C.N.; Koschmieder, S.; Foltz, L.; Guglielmelli, P.; Flindt, T.; Koehler, M.; Mathias, J.; Komatsu, N.; Boothroyd, R.N.; Spierer, A.; Perez, J.; Taylor-Stokes, G.; 57 Waller, J.; Mesa, R.A. The impact of myeloproliferative neoplasms (MPNs) on patient quality of life and productivity: Results from the international MPN Landmark survey. Ann. Hematol. 2017, 96, 1653–1665, doi: 10.1007/s00277-017- 3082-y. 16. Tefferi, A.; Pardanani, A. Myeloproliferative Neoplasms: A Contemporary Review. JAMA Oncol. 2015, 1, 97–105, doi: 10.1001/jamaoncol.2015.89. 17. Meyer, S.; Levine, R.S. Molecular Pathways: Molecular Basis for Sensitivity and Resistance to JAK Kinase Inhibitors. Clin Cancer Res. 2014, 15, 2051–2059, doi:10.1158/1078-0432.CCR-13-0279. 18. Lundberg, P.; Karow, A.; Nienhold, R.; Looser, R.; Hao-Shen, H.; Nissen, I.; Girsberger, S.; Lehmann, T.; Passweg, J.; Stern, M.; Beisel, C.; Kralovics, R.; Skoda, R.C. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood, 2014, 123, 2220–2228, doi: 10.1182/blood- 2013-11-537167. 19. Papaemmanuil, E.; Gerstung, M.; Malcovati, L.; Tauro, S.; Gundem, G.; Van Loo, P.; Yoon, C.J.; Ellis, P.; Wedge, D.C.; Pellagatti, A.; Shlien, A.; Groves, M.J.; Forbes, S.A.; Raine, K.; Hinton, J.; Mudie, L.J.; McLaren, S.; Hardy, C.; Latimer, C.; Della Porta, M.G., O’Meara, S.; Ambaglio, I.; Galli, A.; Butler, A.P.; Walldin, G.; Teague, J.W.; Quek, L.; Sternberg, A.; Gambacorti-Passerini, C.; Cross, N.C.P.; Green, A.R.; Boultwood, J.; Vyas, P.; Hellstrom-Lindberg, E.; Bowen, D.; Cazzola, M.; Stratton, M.R.; Campbell, P.J. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood, 2013, 122, 3616–3627, doi: 10.1182/blood-2013-08-518886. 20. Guglielmelli, P.; Lasho, T.L.; Rotunno, G.; Score, J.; Mannarelli, C.; Pancrazzi, A.; Biamonte, F.; Pardanani, A.; Zoi, K.; Reiter, A.; Duncombe, A.; Fanelli, T.; Pietra, D.; Rumi, E.; Finke, C.; Gangat, N.; Ketterling, R.P.; Knudson, R.A.; Hanson, C.A.; Bosi, A.; Pereira, A.; Manfredini, R.; Cervantes, F.; Barosi, G.; Cazzola, M.; Cross, N.C.P.; Vannucchi, A.M.; Tefferi, A. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: An international study of 797 patients. Leukemia, 2014, 28, 1804–1810, doi: 10.1038/leu.2014.76. 21. Kralovics, R.; Stockton, D.W.; Prchal, J.T. Clonal hematopoiesis in familial polycythemia vera suggests the involvement of multiple mutational events in the early pathogenesis of the disease. Blood. 2003, 102, 3793–3796, doi: 10.1182/blood- 2003-03-0885. 58 22. Rumi, E.; Harutyunyan, A.S.; Pietra, D.; Milosevic, J.D.; Casetti, I.C.; Bellini, M.; Them, N.C.C.; Cavalloni, C.; Ferretti, V.V.; Milanesi, C.; Berg, T.; Sant’Antonio, E.; Boveri, E.; Pascutto, C.; Astori, C.; Kralovics, R.; Cazzola, M. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood. 2014, 123, 2416–2419, doi: 10.1182/blood-2014-01-550434. 23. Landgren, O.; Goldin, L.R.; Kristinsson, S.Y.; Helgadottir, E.A.; Samuelsson, J.; Björkholm, M. Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11,039 patients with myeloproliferative neoplasms in Sweden. Blood. 2008, 112, 2199–2204, doi: 10.1182/blood-2008-03-143602. 24. Langabeer, S.E.; Haslam, K.; Linders, J.; Percy, M.J.; Conneally, E.; Hayat, A.; Hennessy, B.; Leahy, M.; Murphy, K.; Murray, M.; Ni Ainle, F.; Thornton, P.; Sargent, J. Molecular heterogeneity of familial myeloproliferative neoplasms revealed by analysis of the commonly acquired JAK2, CALR and MPL mutations. Fam. Cancer. 2014, 13, 659–663, doi: 10.1007/s10689-014-9743-2. 25. Higgs, J.R.; Sadek, I.; Neumann, P.E.; Ing, V.W.; Renault, N.K.; Berman, J.N.; Greer, W.L. Familial essential thrombocythemia with spontaneous megakaryocyte colony formation and acquired JAK2 mutations. Leukemia. 2008, 22, 1551–1556, doi: 10.1038/leu.2008.115. 26. Aljabry, M. Primary familial and congenital polycythemia; The forgotten entity. J. Appl. Hematol. 2018, 9, 39–43, doi: 10.4103/joah.joah_30_18. 27. Mounier, N. Malignant hematology. Oncologie. 2008, 10, 512–514, doi: 10.1007/s10269-008-0922-3. 28. Milosevic, J.D.; Nivarthi, H.; Gisslinger, H.; Leroy, E.; Rumi, E.; Chachoua, I.; Bagienski, K.; Kubesova, B.; Pietra, D.; Gisslinger, B.; Milanesi, C.; Jäger, R.; Chen, D.; Berg, T.; Schalling, M.; Schuster, M.; Bock, C.; Constantinescu, S.N.; Cazzola, M.; Kralovics, R. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood. 2016, 127, 325– 332, doi: 10.1182/blood-2015-07-661835. 29. de Freitas, R.M.; da Costa Maranduba, C.M. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: An overview. Rev. Bras. Hematol. Hemot. 2015, 37, 348–353, doi: 10.1016/j.bjhh.2014.10.001. 59 30. Tefferi, A.; Barbui, T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis , risk-stratification and management. Am. J. Hematol. 2019, 2, 133–143, doi: 10.1002/ajh.25303. 31. Vainchenker, W.; Kralovics, R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017, 129, 667–679, doi: 10.1182/blood-2016-10-695940.subtypes. 32. Bousoik, E.; Aliabadi, H.M. Do We Know Jack2 About JAK ? A Closer Look at JAK/STAT Signaling Pathway. Front. Oncol. 2018, 8, 1–20, doi: 10.3389/fonc.2018.00287. 33. Milosevic, J.D., Schischlik, F.; Jäger, R.; Ivanov, D.; Eisenwort, G.; Keller, A.; Schuster, M.; Hadzijusufovic, E.; Krauth, M.; Spörk, R.; Gisslinger, B.; Koller, E.; Fillitz, M.; Pfeilstocker, M.; Sliwa, T.; Keil, F.; Bock, C.; Gisslinger, H.; Kralovics, R.; Valent, P. Overexpression of PD-L1 Correlates with JAK2-V617F Mutational Burden and Is Associated with Chromosome 9p Uniparental Disomy in MPN. Blood. 2020, 136, doi: 10.1182/blood-2020-137447. 34. Koschmieder, S.; Mughal, T.; Hasselbalch, H.C.; Barosi, G.; Valent, P.; Kiladjian, J.; Jeryczynski,G.; Gisslinger, H.; Jutzi, J.S.; Pahl, H.L.; Hehlmann, R.; Vannucchi, A.M.; Cervantes, F.; Silver. R.T.; Barbui, T. Myeloproliferative neoplasms and inflammation: Whether to target the malignant clone or the inflammatory process or both. Leukemia. 2016, 30, 1018–1024, doi: 10.1038/leu.2016.12. 35. Gleitz, H.; Dugourd, A.J.F.; Leimkuhler, N.B.; Snoeren, I.A.M.; Fuchs, S.N.; Menzel, S.; Ziegler, S.; Kroger, N.; Triviai, I.; Busche, G.; Kreipe, H.; Banjanin, B.; Pritchard, J.E.; Hoogenboezem, R.; Bindels, E.M.; Schumacher, N.; Rose-John, S.; Elf, S.; Saez-Rodriguez, J.; Kramann, R.; Schneider, R.K. Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood. 2020, 136, 2051–2064, doi: 10.1182/blood.2019004095. 36. Verstovsek, S.; Manshouri, T.; Pilling, D.; Bueso-Ramos, C.E.; Newberry, K.J.; Prijic, S.; Knez, L.; Bozinovic, K.; Harris, D.M.; Spaeth, E.L.; Post, S.M.; Multani, A.S.; Rampal, R.K.; Ahn, J.; Levine, R.L.; Creighton, C.J.; Kantarjian, H.M.; Estrov, E. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis. J. Exp. Med. 2016, 213, 1723–1740, doi: 10.1084/jem.20160283. 37. Baxter, E.J.; Scott, L.M.; Campbell, P.J.; East, C.; Fourouclas, N.; Swanton, S.; Vassiliou, G.S.; Bench, A.J.; Boyd, E.M.; Curtin, N.; Scott, M.A.; Erber, W.N.; 60 Green, A.R. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005, 365, 1054–1061, doi: 10.1016/S0140- 6736(05)74230-6. 38. Levine, R.L.; Wadleigh, M.; Cools, J.; Ebert, B.L.; Wernig, G.; Huntly, B.J.P.; Boggon, T.J.; Wlodarska, I.; Clark, J.J.; Moore, S.; Adelsperger, J.; Koo, S.; Lee, J.C.; Gabriel, S.; Mercher, T.; D’Andrea, A.; Fröhling, S.; Döhner, K.; Marynen, P.; Vandenberghe, P.; Mesa, R.A.; Tefferi, A.; Griffin, J.D.; Eck, M.J.; Sellers, W.R.; Meyerson, M.; Golubb, T.D.; Lee, S.J.; Gilliland, D.G. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005, 7, 387–397, doi: 10.1016/j.ccr.2005.03.023. 39. Kralovics, R.; Passamonti, F.; Buser, A.S.; Teo, S.-S.; Tiedt, R.; Passweg, J.R.; Tichelli, A.; Cazzola, M.; Skoda, R.C. A Gain-of-Function Mutation of JAK2 in Myeloproliferative Disorders. N Engl J Med. 2005, 352, 1779–1790, doi: 10.1056/NEJMoa051113. 40. James, C.; Ugo,V.; Le Couédic, J.P.; Staerk, J.; Delhommeau, F.; Lacout, C.; Garçon, L.; Raslova, H.; Berger, R.; Bennaceur-Griscelli, A.; Villeval, J.L.; Constantinescu, S.N.; Casadevall, N.; Vainchenker, W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005, 434, 1144–1148, doi: 10.1038/nature03546. 41. Abdulqader, A.; Saeed, B.; Getta, H.A.; Khoshnaw, N.; Abdulqader, G.; Mohammed, A. Prevalence of JAK2 V617F, CALR, and MPL W515L Gene Mutations in Patients with Essential Thrombocythemia in Kurdistan Region of Iraq. Korean, J. Clin. Lab. Sci. 2021, 53, 41–48, doi: 10.15324/kjcls.2021.53.1.41. 42. Staerk, J.; Constantinescu, S.N. The JAK-STAT pathway and hematopoietic stem cells from the JAK2 V617F perspective. JAK-STAT. 2012, 1, 184—190, doi: 10.4161/jkst.22071. 43. Hermouet, S.; Vilaine, M. The JAK2 46/1 haplotype: A marker of inappropriate myelomonocytic response to cytokine stimulation, leading to increased risk of inflammation, myeloid neoplasm, and impaired defense against infection?. Haematologica. 2011, 96, 1575–1579, doi: 10.3324/haematol.2011.055392. 44. Olcaydu, D.; Rumi, E.; Harutyunyan, A.; Passamonti, F.; Pietra, D.; Pascutto, C.; Berg, T.; Jäger, R.; Hammond, E.; Cazzola, M.; Kralovics, R. The role of the JAK2 61 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms. Haematologica. 2011, 96, 367–374, doi: 10.3324/haematol.2010.034488. 45. Jones, A.V.; Cross, N.C.P. Inherited predisposition to myeloproliferative neoplasms. Ther. Adv. Hematol. 2013, 4, 237–253, doi: 10.1177/2040620713489144. 46. Tashi, T.; Swierczek, S.; Prchal, J.T. Familial MPN Predisposition.. Curr. Hematol. Malig. Rep. 2017, 12, 442–447, doi: 10.1007/s11899-017-0414-x. 47. Koh, S.P.; Yip, S.P.; Lee, K.K.; Chan, C.C.; Lau, S.M.; Kho, C.S.; Lau, C.K.; Lin, S.Y.; Lau, Y.M.; Wong, L.G.; Au, K.L.; Wong, K.F.; Chu, R.W.; Yu, P.H.; Chow, E.Y.; Leung, K.F.; Tsoi., W.C.; Yung, B. Genetic association between germline JAK2polymorphisms and myeloproliferative neoplasms in Hong Kong Chinese population: A case–control study. BMC Genet. 2014, 15, 1–12, doi: 10.1186/s12863- 014-0147-y. 48. Hinds, D.A.; Barnholt, K.E.; Mesa, R.A.; Kiefer, A.K.; Do, C.B.; Eriksson, N.; Mountain, J.L.; Francke, U.; Tung, J.Y.; Nguyen, H.; Zhang, H.; Gojenola, L.; Zehnder, J.L.; Gotlib, J. Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. Blood. 2016, 128, 1121–1128, doi: 10.1182/blood-2015-06-652941. 49. Owen, K.L.; Brockwell, N.K.; ParkerImmune, B.S. JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression. Cancers. 2019, 11, 1–26, doi:10.3390/cancers11122002. 50. 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. Int. J. Mol. Sci. 2021, 22, 1–14, doi: 10.3390/ijms22031143. 51. Landolfi, R.; Di Gennaro, L. Pathophysiology of thrombosis in myeloproliferative neoplasms. Haematologica. 2011, 96, 183–186, doi: 10.3324/haematol.2010.038299. 52. Wang, W.; Liu, W.; Fidler, T.; Wang, Y.; Tang, Y.; Woods, B.; Welch, C.; Cai, B.; Silvestre-Roig, C.; Ai, D.; Yang, Y.G.; Hidalgo, A.; Soehnlein, O.; Tabas, I.; Levine, R.L.; Tall, A.R.; Wang, N. Macrophage inflammation, erythrophagocytosis, and accelerated atherosclerosis in JAK2V617F mice. Circ. Res. 2018, 123, 35–47, doi: 10.1161/CIRCRESAHA.118.313283. 53. Marin Oyarzún, C.P.; Heller, P.G. Platelets as mediators of thromboinflammation in chronic myeloproliferative neoplasms. Front. Immunol. 2019, 10, 1–9, doi: 10.3389/fimmu.2019.01373. 62 54. Vannucchi, A.M.; Guglielmelli, P. What are the current treatment approaches for patients with polycythemia vera and essential thrombocythemia?. Hematology. 2017, 1, 480–488, doi: 10.1182/asheducation-2017.1.480. 55. Wolach, O.; Abulafia, A.S. Can Novel Insights into the Pathogenesis of Myeloproliferative Neoplasm-Related Thrombosis Inform Novel Treatment Approaches?. Hemato. 2021, 2, 305–328, doi: 10.3390/hemato2020018. 56. Marín, C.P.; Glembotsky, A.C.; Goette, N.P.; Lev, P.R.; de Luca, G.; Baroni, M.C.; Moiraghi, B.; Castro, M.A.; Vicente, A.; Marta, R.F.; Schattner, M.; Heller, P.G. Platelet Toll-Like Receptors Mediate Thromboinflammatory Responses in Patients With Essential Thrombocythemia. Front. Immunol. 2020, 11, 1–12, doi: 10.3389/fimmu.2020.00705. 57. Di Rosa, M.; Giallongo, C.; Romano, A.; Li Volti, G.; Musumeci, G.; Barbagallo, I.; Castrogiovanni, P.; Palumbo, G.A. Immunoproteasome genes are modulated in CD34+ JAK2V617F mutated cells from primary myelofibrosis patients. Int. J. Mol. Sci. 2020, 21, 1–19, doi: 10.3390/ijms21082926. 58. Davis, Z.; Felices, M.; Lenvik, T.; Badal, S.; Walker, J.T.; Hinderlie, P.; Riley, J.L.; Vallera, D.A.; Blazar, B.R.; Miller, J.S. Low-density PD-1 expression on resting human natural killer cells is functional and upregulated after transplantation. Blood adv. 2021, 5, 1069–1080, doi: 10.1182/bloodadvances.2019001110. 59. Perner, F.; Perner, C.; Ernst, T.; Heidel, F.H. Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation. Cells. 2019, 8, 1–19, doi:10.3390/cells8080854. 60. Prestipino, A.; Emhardt, A.J.; Aumann, K.; O’Sullivan, D.; Gorantla, S.P.; Duquesne, S.; Melchinger, W.; Braun, L.; Vuckovic, S.; Boerries, M.; Busch, H.; Halbach, S.; Pennisi, S.; Poggio, T.; Apostolova, P.; Veratti, P.; Hettich, M.; Niedermann, G.; Bartholomä, M.; Shoumariyeh, K.; Jutzi, J.S.; Wehrle, J.; Dierks, C.; Becker, H.; Schmitt-Graeff, A.; Follo, M.; Pfeifer, D.; Rohr, J.; Fuchs, S.; Ehl, S.; Hartl, F.A.; Minguet, S.; Miething, C.; Heidel, F.H.; Kröger, N.; Triviai, I.; Brummer, T.; Finke, J.; Illert, A.L.; Ruggiero, E. Oncogenic JAK2V617F causes PD- L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med. 2019, 10, 1–25, doi: 10.1126/scitranslmed.aam7729.Oncogenic. 61. Ginzburg, Y.Z.; Feola, M.; Zimran, E.; Varkonyi, J.; Ganz, T.; Hoffman, R. Dysregulated iron metabolism in polycythemia vera : Etiology and consequences. Leukemia. 2018, 32, 2105–2116, doi: 10.1038/s41375-018-0207-9. 63 62. Allain-Maillet, S.; Bosseboeuf, A.; Mennesson, N.; Bostoën, M.; Dufeu, L.; Choi, E.H.; Cleyrat, C.; Mansier, O.; Lippert, E.; Le Bris, J.; Gombert, J.M.; Girodon, F.; Pettazzoni, M.; Bigot-Corbel, E.; Hermouet, S. Anti-Glucosylsphingosine Autoimmunity, JAK2V617F-Dependent Interleukin-1β and JAK2V617F- Independent Cytokines in Myeloproliferative Neoplasms. Cancers. 2020, 12, 1–24, doi:10.3390/cancers12092446. 63. Hermouet, S.; Bigot-Corbel, E.; Gardie, B. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation. Mediators Inflamm. 2015, 1-16, doi: 10.1155/2015/145293. 64. Oyarzún, C.; Carestia, A.; Lev, P.R.; Glembotsky, A.C.; Castro, M.A.; Moiraghi, B.; Molinas, F.C.; Marta, R.F.; Schattner, M.; Heller, P.G. Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms. Sci. Rep. 2016, 6, 1–13, doi: 10.1038/srep38738. 65. Wolach, O.; Sellar, R.S.; Martinod, K.; Cherpokova, D.; McConkey, M.; Chappell, R.J.; Silver, A.J.; Adams, D.; Castellano, C.A.; Schneider, R.K.; Padera, R.F.; DeAngelo, D.J.; Wadleigh, M.; Steensma, D.P.; Galinsky, I.; Stone, R.M.; Genovese, G.; McCarroll, G.A.; Iliadou, B.; Hultman, C.; Neuberg, D.; Mullally, A.; Wagner, D.D.; Ebert1, B.L. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci. Transl. Med. 2018, 10, 1–11, doi: 10.1126/scitranslmed.aan8292. 66. Oh, S.T. Neutralize the neutrophils! Neutrophil β1/β2 integrin activation contributes to JAK2-V617F–driven thrombosis. J. Clin. Invest. 2018, 128, 4248–4250, doi: 10.1172/JCI123388. 67. Gupta, N.; Edelmann, B.; Schnoeder, T.M.; Saalfeld, F.C.; Wolleschak, D.; Kliche, S.; Schraven, B.; Heidel, F.H.; Fischer, T. JAK2-V617F activates β1-integrin- mediated adhesion of granulocytes to vascular cell adhesion molecule. Leukemia. 2017, 31, 1223–1226, doi: 10.1038/leu.2017.26. 68. Edelmann, B.; Gupta, N.; Schnoeder, T.M.; Oelschlegel, A.M.; Shahzad, K.; Goldschmidt, J.; Philipsen, L.; Weinert, S.; Ghosh, A.; Saalfeld, F.C.; Nimmagadda, S.C.; Müller, P.; Braun-Dullaeus, R.; Mohr, J.; Wolleschak, D.; Kliche, S.; Amthauer, H.; Heidel, F.H.; Schraven, B.; Isermann, B.; Müller, A.J.; Fischer, T. JAK2-V617F promotes venous thrombosis through β1/β2 integrin activation. J. Clin. Invest. 2018, 128, 4359–4371, doi: 10.1172/JCI90312 69. Haage, T.R.; Müller, A..J.; Arunachalam, P.; Fischer, T. Reveal the Neutrophil: Elucidating the Role of a Neutrophil-Specific JAK2-V617F Mutation. Blood. 2019, 134, 2965, doi: 10.1182/blood-2019-122660. 70. Gaertner, F.; Massberg, S. Blood coagulation in immunothrombosis—At the frontline of intravascular immunity. Semin. Immunol. 2016, 28, 561–569, doi: 10.1016/j.smim.2016.10.010. 71. Shi, C.; Yang, L.; Braun, A.; Anders, H.J. Extracellular DNA—A Danger Signal Triggering Immunothrombosis. Front. Immunol. 2020, 11, 1–15, doi: 10.3389/fimmu.2020.568513. 72. Yang, J.; Wu, Z.; Long, Q.; Huang, J.; Hong, T.; Liu, W.; Lin, J. Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13. Front. Immunol. 2020, 11, 1–16, doi: 10.3389/fimmu.2020.610696. 73. McKenna, E.; Mhaonaigh, A.U.; Wubben, R.; Dwivedi, A.; Hurley, T.; Kelly, L.A.; Stevenson, N.J.; Little, M.A.; Molloy, E.J. Neutrophils: Need for Standardized Nomenclature. Front. Immunol. 2021, 12, 1–14, doi: 10.3389/fimmu.2021.602963. 74. Shaul, M.E.; Fridlender, Z.G. Cancer-related circulating and tumor-associated neutrophils – subtypes, sources and function. FEBS J. 2018, 285, 4316–4342, doi: 10.1111/febs.14524. 75. Giese, M.A.; Hind, L.E.; Huttenlocher, A. Neutrophil plasticity in the tumor microenvironment. Blood. 2019, 133, 2159–2167, doi: 10.1182/blood-2018-11- 844548. 76. Masucci, M.T.; Minopoli, M.; Carriero, M.V. Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy. Front. Oncol. 2019, 9, 1–16, doi: 10.3389/fonc.2019.01146. 77. Piccard, H.; Muschel, R.J.; Opdenakker, G. On the dual roles and polarized phenotypes of neutrophils in tumor development and progression. Crit. Rev. Oncol. Hematol. 2012, 82, 296–309, doi: 10.1016/j.critrevonc.2011.06.004. 78. Podaza, E.; Risnik, D. Neglected players: Tumor associated neutrophils involvement in chronic lymphocytic leukemia progression. Oncotarget. 2019, 10, 1862–1863, doi: 10.18632/oncotarget.26716. 79. Castiglione, M.; Jiang, Y.P.; Mazzeo, C.; Lee, S.; Chen, J.S.; Kaushansky, K.; Yin, W.; Lin, R.Z.; Zheng, H.; Zhan, H. Endothelial JAK2V617F mutation leads to thrombosis, vasculopathy, and cardiomyopathy in a murine model of 65 myeloproliferative neoplasm,” J. Thromb. Haemost., 2020, 18, 3359–3370, doi: 10.1111/jth.15095. 80. Conran, N.; de Paula, E.V. Thromboinflammatory mechanisms in sickle cell disease – challenging the hemostatic balance. Haematologica. 2020, 105, 2380–2390, doi: 10.3324/haematol.2019.239343. 81. Poisson, J.; Tanguy, M.; Davy, H.; Camara, F.; El Mdawar, M.B.; Kheloufi, M.; Dagher, T.; Devue, C.; Plessier, J.A.; Merchant, S.; Blanc-Brude, O.; Souyri, M.; Mougenot, N.; Dingli, F.; Loew, D.; Hatem, S.N.; James, C.; Villeval, J.L.; Boulanger, C.M.; Rautou, P.E. Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm. J. Clin. Invest. 2020, 130, 2630–2643, doi: https://www.jci.org/articles/view/124566. 82. Murata, M. Inflammation and cancer. Environ. Health Prev. Med. 2018, 23, 1–8, doi: 10.1186/s12199-018-0740-1. 83. Lussana, F.; Rambaldi, A. Inflammation and myeloproliferative neoplasms. J. Autoimmun. 2017, 85, 1–6, doi: 10.1016/j.jaut.2017.06.010. 84. Arellano-Rodrigo, E.; Alvarez-Larra, A.; Reverter, J.C.; Colomer, D.; Villamor, N.; Bellosillo, B.; Cervantes, F. Platelet turnover, coagulation factors, and soluble markers of platelet and endothelial activation in essential thrombocythemia : Relationship with thrombosis occurrence and JAK 2 V617F allele burden. Am. J. Hematol. 2008, 84, 102–108, doi: 10.1002/ajh.21338. 85. Kaifie, A.; Kirschner, M.; Wolf, D.; Maintz, C.; Hänel, M.; Gattermann, N.; Gökkurt, E.; Platzbecker, U.; Hollburg, W.; Göthert, J.R.; Parmentier, S.; Lang, F.; Hansen, R.; Isfort, S.; Schmitt, K.; Jost, E.; Serve, H.; Ehninger, G.; Berdel, W.E.; Brümmendorf, T.H.; Koschmieder, S. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): Analysis from the German SAL-MPN- registry. J. Hematol. Oncol. 2016, 9, 1–11, doi: 10.1186/s13045-016-0242-9. 86. Yonal-Hindilerden, I.; Daglar-Aday, A.; Akadam-Teker, B.; Yilmaz, C.; Nalcaci, M.; Yavuz, A.S.; Dargin, D. Mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms. J. Blood Med. 2015, 6, 157– 176, doi: 10.2147/JBM.S78826. 87. Matsuura, S.; Thompson, C.R.; Belghasem, M.E.; Bekendam, R.H.; Piasecki, A.; Leiva, O.; Ray, A.; Italiano, J.; Yang, M.; Merill-Skoloff, G.; Chitalia, V.C.; Flaumenhaft, R.; Ravid, K. Platelet dysfunction and thrombosis in JAK2V617F- 66 mutated primary myelofibrotic mice. Arterioscler. Thromb. Vasc. Biol. 2020, 40, 262–272, doi: 10.1161/ATVBAHA.120.314760. 88. Greenfield, G.; McMullin, M.F.; Mills, K. Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol. 2021, 14, 1–18, doi: 10.1186/s13045-021-01116-z. 89. Leimk€uhler, N.B.; Gleitz, H.F.E.; Ronghui, L.; Snoeren, I.A.M.; Fuchs, S.N.R.; Nagai, J.S.; Banjanin, B.; Lam, K.H.; Vogl, T.; Kuppe, C.; Stalmann, U.S.A., Busche, G.; Kreipe, H.; Gutgemann, I.; Krebs, P.; Banz, Y.; Boor, P.; Wing-Yin Tai, E.; Brummendorf, T.H.; Koschmieder, S.; Crysandt, M.; Bindels, E.; Kramann, R.; Costa, I.G.; Schneider, R.K. Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis. Cell Stem Cell. 2021, 28, 637–652, doi: 10.1016/j.stem.2020.11.004. 90. Goette, N.P.; Lev, P.R.; Heller, P.G.; Kornblihtt, L.I.; Korin, L.; Molinas, F.C.; Marta, R.F. Monocyte IL-2Rα expression is associated with thrombosis and the JAK2V617F mutation in myeloproliferative neoplasms. Cytokine. 2010, 51, 67–72, doi: 10.1016/j.cyto.2010.04.011. 91. Margraf, A.; Zarbock, A. Platelets in Inflammation and Resolution. J. Immunol. 2019, 203, 2357–2367, doi: 10.4049/jimmunol.1900899. 92. Brostjan, C.; Oehler, R. The role of neutrophil death in chronic inflammation and cancer. Cell Death Discov. 2020, 6, 1–8, doi: 10.1038/s41420-020-0255-6. 93. xun Wang, L.; xi Zhang, S.; Wu, H.J.; lu Rong, X.; Guo, J. M2b macrophage polarization and its roles in diseases. J. Leukoc. Biol. 2019, 106, 345–358, doi: 10.1002/JLB.3RU1018-378RR. 94. Molitor, D.C.; Boor, P.; Buness, A.; Schneider, R.K.; Teichmann, L.L.; Körber, R.M.; Horvath, G.L.; Koschmieder, S.; Gütgemann, I. Macrophage frequency in the bone marrow correlates with morphologic subtype of myeloproliferative neoplasm. Ann. Hematol. 2021, 100, 97–104, doi: 10.1007/s00277-020-04304-y. 95. Larsen, T.S.; Christensen, J.H.; Hasselbalch, H.C.; Pallisgaard, N. The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders. Br. J. Haematol. 2007, 36, 745–751, doi: 10.1111/j.1365-2141.2007.06497.x. 96. Nicolosi, M.; Mudireddy, M.; Gangat, N.; Pardanani, A.; Hanson, C.A.; Ketterling, R.P.; Tefferi, A. Normal karyotype in myelofibrosis: Is prognostic integrity affected 67 by the number of metaphases analyzed?. Blood Cancer J. 2018, 8, 1–5 , 2018, doi: 10.1038/s41408-017-0046-3. 97. Tefferi, A.; Nicolosi, M.; Mudireddy, M.; Lasho, T.L.; Gangat, N.; Begna, K.H.; Hanson, C.A.; Ketterling, R.P.; Pardanani, A. Revised cytogenetic risk stratification in primary myelofibrosis: Analysis based on 1002 informative patients. Leukemia. 2018, 32, 1189–1199, doi: 10.1038/s41375-018-0018-z. 98. Gonzalez-Rodriguez, A.P.; Villa-Álvarez, M.; Sordo-Bahamonde, C.; Lorenzo- Herrero, S.; Gonzalez, S. NK Cells in the Treatment of Hematological Malignancies. J. Clin. Med. 2019, 8, 1–23, doi: 10.3390/jcm8101557. 99. Arantes, A.; Leal, C.; Araújo, C.; Santos, P.; Bergamo, A.; Welner, R.S.; Tenen, D.G.; Mullally, A.; Kobayashi, S.; Magalhaes, E.; Lobo, L. Decreased Activity of NK Cells in Myeloproliferative Neoplasms. Blood. 2015, 126, 1637, doi: 10.1182/blood.V126.23.1637.1637. 100. Palumbo, G.A.; Stella, S.; Pennisi, M.S.; Pirosa, C.; Fermo, E.; Fabris, S.; Cattaneo, D.; Iurlo, A. The Role of New Technologies in Myeloproliferative Neoplasms. Front. Oncol. 2019, 9, 1–10, doi: 10.3389/fonc.2019.00321. 101. Helbig , G. Classical Philadelphia-negative myeloproliferative neoplasms: Focus on mutations and JAK2 inhibitors. Med. Oncol. 2018, 35, 1–7, doi: 10.1007/s12032- 018-1187-3. 102. Skov, V. Next Generation Sequencing in MPNs. Lessons from the Past and Prospects for Use as Predictors of Prognosis and Treatment Responses. Cancers. 2021, 12, 1– 38, doi:10.3390/cancers12082194. 103. Patnaik, M.M.; Lasho, T.L. Genomics of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes. Hematology. 2020, 20, 450–459, doi: 10.1182/HEMATOLOGY.2020000130. 104. Luque Paz, D.; Jouanneau-Courville, R.; Riou, J.; Ianotto, J.C.; Boyer, F.; Chauveau, A.; Renard, M.; Chomel, J.C.; Cayssials, E.; Gallego-Hernanz, M.P.; Pastoret, C.; Murati, A.; Courtier, F.; Rousselet, M.C.; Quintin-Roue, I.; Cottin, L.; Orvain, C.; Thepot, S.; Chretien, J.M.; Delneste, Y.; Ifrah, N.; Blanchet, O.; Hunault-Berger, M.; Lippert, E.; Ugo, V. Leukemic evolution ofpolycythemia vera and essential thrombocythemia: Genomic profiles predict time to transformation. Blood adv. 2020, 4, 4887–4897, doi: 10.1182/bloodadvances.2020002271. 68 105. Vannucchi, A.M. From leeches to personalized medicine: Evolving concepts in the management of polycythemia vera. Haematologica. 2017, 102, 18–29, doi: 10.3324/haematol.2015.129155. 106. Moliterno, A.; Kaizer, H. Applied genomics in MPN presentation. Hematology. 2020, 2020, 434–439, doi: 10.1182/hematology.2020000128. 107. Downes, C.E.J.; McClure, B.J.; Rehn, J.; Breen, J.; Bruning, J.B.; Yeung, D.T.; White, D.L. Acquired Mutations within the JAK2 Kinase Domain Confer Resistance to JAK Inhibitors in an in Vitro model of a High-Risk Acute Lymphoblastic Leukemia. Blood. 2020, 136, 5–6, doi: 10.1182/blood-2020-133491. 108. Helbig, G.; Wichary, R.; Torba, K.; Kyrcz-Krzemien, S. Resolution of thrombocytopenia, but not polycythemia after ruxolitinib for polycythemia vera with detectable mutation in the exon 12 of the JAK2 gene. Med. Oncol. 2017, 34, 31. [CrossRef] 109. Habbel, J.; Arnold, L.; Chen, Y.; M. ̈ollmann, M.; Bruderek, K.; Brandau, S.; D. ̈uhrsen, U.; Hanoun, M. Inflammation-driven activation of JAK/STAT signaling reversibly accelerates acute myeloid leukemia in vitro. Blood adv. 2020, 4, 3000– 3010, doi: 10.1182/bloodadvances.2019001292. 110. Forte, D.; Barone, M.; Palandri, F.; Catani, L. The “Vesicular Intelligence” Strategy of Blood Cancers. Genes. 2021, 12, 1–29, doi: 10.3390/genes12030416. 111. Garcia-Gisbert, N.; Fernandez-Ibarrondo, L.; Fernandez-Rodrıguez, C.; Gibert, J.; Andrade- Campos, M.; Arenillas, L.; Camacho, L.; Angona, A.; Longaron, R.; Salar, A.; Calvo, X.; Besses, C.; Bellosillo, B. Circulating cell-free DNA improves the molecular characterisa- tion of Ph-negative myeloproliferative neoplasms. Br. J. Haematol. 2021, 192, 300–309, doi: 10.1111/bjh.17087. 112. Găman, M.A.; Cozma, M.A.; Dobrică, E.C.; Cretoiu, S.M.; Găman, A.M.; Diaconu, C.C. Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia- Negative Classical Myeloproliferative Neoplasms: A Systematic Review. Life. 2021, 11, 1–23, doi: 10.3390/life1107067pt_BR
dc.publisher.initialsUEApt_BR
Appears in Collections:DISSERTAÇÃO - PPCAH Programa de Pós-Graduação em Ciências Aplicadas à Hematologia

Files in This Item:
File Description SizeFormat 
Caracterização molecular de variantes no gene JAK2 em pacientes com neoplasias mieloproliferativas crônicas BCR ABL1 negativo.pdf3,18 MBAdobe PDFView/Open
Show simple item record


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.