Platelets as mediators of Thromboinflammation in chronic Myeloproliferative Neoplasms

Chronic myeloproliferative neoplasms (MPN) are stem cell disorders driven by mutations in JAK2, CALR, or MPL genes and characterized by myeloid proliferation and increased blood cell counts. They encompass three closely related conditions, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Elevated levels of cytokines released by clonal and non-clonal cells generate a chronic proinflammatory state that contributes to disease pathogenesis. Thrombosis represents the most common cause of morbidity and mortality in MPN, although paradoxically, patients may also present with a bleeding diathesis. The mechanisms leading to thrombosis are complex and multiple and include increased blood cells together with qualitative abnormalities of red cells, leukocytes, and platelets that favor a prothrombotic activated phenotype. The functional interplay between blood cells, the clotting cascade, and dysfunctional endothelium contributes to hypercoagulability and this process is perpetuated by the effect of inflammatory cytokines. In addition to their well-known function in hemostasis, platelets contribute to innate immunity and inflammation and play a key role in MPN thromboinflammatory state. In vivo platelet activation leads to platelet aggregate formation and exposure of adhesion molecules which favor their interaction with activated neutrophils and monocytes leading to circulating platelet-leukocyte heterotypic aggregates. Platelets are recruited to the activated endothelium further enhancing the reciprocal activation of both cell types. Crosstalk between activated cells drives cytokine production, further fuelling the self-reinforcing thromboinflammatory loop. In addition, MPN platelets provide a procoagulant scaffold which triggers the coagulation cascade and platelet-derived microparticles amplify this response. Markers of platelet, leukocyte, endothelial and coagulation activation are increased in MPN patients although prospective studies are required to determine the potential value of these parameters for identifying patients at increased thrombotic risk. Thrombosis remains the main complication of MPN patients, with a high risk of recurrence despite adequate cytoreductive and antithrombotic treatment. Deeper insight into the mechanism favoring thrombosis development in this setting may lead to novel therapeutic approaches for MPN thrombosis. Considering the critical role of inflammation in the vascular risk, concomitant targeting of inflammatory pathways could potentially impact on primary or secondary prevention strategies.Fil: Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Estudio molecular en Neoplasias Mieloproliferativas Crónicas: mutación JAK2V617F

La mutación JAK2V617F constituye la alteración molecular más frecuente en Neoplasias Mieloproliferativas Crónicas BCR-ABL-negativas, detectándose en > 95% de los pacientes con Policitemia Vera y alrededor de 50-60% de aquellos con Mielofibrosis Primaria y Trombocitemia Esencial. Constituye un marcador clonal, siendo su utilidad diagnóstica principal la diferenciación entre desórdenes neoplásicos y condiciones reactivas. Además de las Neoplasias Mieloproliferativas BCR-ABL-negativas, puede detectarse con menor frecuencia en otras Neoplasias Mieloides. Los pacientes con Trombocitemia Esencial portadores de esta mutación presentan un moderado incremento en el riesgo trombótico, si bien su presencia no constituye por sí misma un parámetro que determine la decisión terapéutica. Hasta el presente, si bien se ha descripto mayor riesgo de trombosis y transformación a mielofibrosis en los pacientes con niveles más elevados de carga alélica JAK2V617F, la utilidad de su medición en el manejo clínico o el monitoreo del tratamiento en los pacientes con Neoplasias Mieloproliferativas no es clara.The JAK2V617 mutation is the most frequent molecular abnormality underlying the pathogenesis of chronic myeloproliferative neoplasmas. More than 95% of patients with polycythemia vera and around half of those with essential thrombocythemia and primary myelofibrosis carry this mutation. It is useful to distinguish clonal from reactive conditions and is one of the diagnostic criteria included in the WHO classification. It may be detected, albeit with low frequency, in other myeloid neoplasms. Although a moderate increase in the thrombotic risk has been described for JAK2V617F-positive essential thrombocythemia patients, its presence does not represent by itself a parameter to guide treatment recommendations. Patients with high JAK2V617F allelic burden have increased risk of thrombosis and myelofibrotic transformation. However, the role of allele burden measurement in the clinical management and treatment monitoring of patients with myeloproliferative neoplasms remains to be determined.Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; ArgentinaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas; Argentin

A deep dive into the pathology of gray platelet syndrome: new insights on immune dysregulation

The gray platelet syndrome (GPS) is a rare platelet disorder, characterized by impaired alpha-granule biogenesis in megakaryocytes and platelets due to NBEAL2 muta-tions. Typical clinical features include macrothrombocytopenia, bleeding and elevated vita-min B12 levels, while bone marrow fibrosis and splenomegaly may develop during disease progression. Recently, the involvement of other blood lineages has been highlighted, reveal-ing the role of NBEAL2 outside the megakaryocyte-platelet axis. Low leukocyte counts, decreased neutrophil granulation and impaired neutrophil extracellular trap formation repre-sent prominent findings in GPS patients, reflecting deranged innate immunity and associated with an increased susceptibility to infection. In addition, low numbers and impaired degra-nulation of NK cells have been demonstrated in animal models. Autoimmune diseases involving different organs and a spectrum of autoantibodies are present in a substantial proportion of GPS patients, expanding the syndromic spectrum of this disorder and pointing to dysregulation of the adaptive immune response. Low-grade inflammation, as evidenced by elevation of liver-derived acute-phase reactants, is another previously unrecognized feature of GPS which may contribute to disease manifestations. This review will focus on the mechanisms underlying the pathogenesis of blood cell abnormalities in human GPS patients and NBEAL2-null animal models, providing insight into the effects of NBEAL2 in hemos-tasis, inflammation and immunity.Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: de Luca, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Comunicação e memória em textos de coletivos de teatro feminista no Brasil: Boneca de pano (SC, 2014) e Entre Nós: buzinas, chicotes e ácidos (CE, 2017)

Although feminist movements began more than a hundred years ago in Brazil, there are still few Brazilian groups that develop dramaturgy written by and for women, even considering amateur theater. We present in this article the analysis of two theatrical texts (or scripts), still unpublished: Boneca de pano, by the Santa Catarina theater collective (Em) Companhia de Mulheres, and Entre Nós: buzinas, chicotes e ácidos, by the Ceará collective Arremate de Teatro. We aim to understand, when comparing these two theatrical narratives, similarities and differences of the themes in question, considering their places of production, as well as their origins. We start from the hypothesis that theatrical narratives written by collectives that consider themselves feminists function as an authorized space for Brazilian women to speak, for the identification and rupture of behaviors inherited from the patriarchal culture. We confirm, based on the theoretical frame of theater, discourse analysis, cultural studies, gender studies and social memory, that the two texts under analysis present themselves as equally potent forms of catharsis, sensitization and resistance to the domestication and oppression to which women are still submitted.Apesar de os movimentos feministas terem se iniciado há mais de cem anos no Brasil, ainda são poucos os grupos brasileiros que desenvolvem dramaturgia escrita por e para mulheres, ainda que se considere o teatro amador. Apresentamos neste artigo a análise de dois textos teatrais (ou roteiros), ainda inéditos: Boneca de pano, do coletivo de teatro catarinense (Em) Companhia de Mulheres, e Entre Nós: buzinas, chicotes e ácidos, do coletivo cearense Arremate de Teatro. Temos como objetivo compreender, ao compararmos essas duas narrativas teatrais, semelhanças e diferenças dos temas em pauta, considerando seus locais de produção, bem como suas origens. Partimos da hipótese de que narrativas teatrais redigidas por coletivos que se assumem feministas funcionam como um espaço autorizado de fala das brasileiras, de identificação e de ruptura de comportamentos herdados da cultura patriarcal. Confirmamos, a partir dos suportes teóricos sobre teatro, análise do discurso, estudos culturais, de gênero e memória social, que os dois textos em tela se apresentam como formas igualmente potentes de catarse, sensibilização e resistência à domesticação e à opressão a que as mulheres ainda são submetidas

Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-antibodies

Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon.Fil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Grodzielski, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Contrufo, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pierdominici, Marta S.. Departamento de Hematología, Hospital Ramos Mejía, Buenos Aires, Argentina; ArgentinaFil: Espasandin, Yesica Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Riveros, Dardo Alberto. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: García, Alejandro Jorge. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Memórias, metáforas e imaginação em narrativas orais de história de vida

We present the discussion of the imaginative character in life story narratives recorded by methods such as Oral History, considered scientific research resources. We propose the following questions: How do we deal with the imagination and metaphors in oral narratives of life stories? How do we regard the demand for “truth” in texts that activate subjectivity? Individual and subjective memories confer scientificity to narratives? We place the problem of truth and its relationship to language and knowledge, with Friedrich Nietzsche and Mikhail Bakhtin. We articulate theoretical review and case report, considering mental images as media that convey memories and, for this reason, a field of studies for Communication and History.Discutimos o caráter imaginativo de narrativas de histórias de vida registradas por métodos como a História Oral, consideradas fontes de pesquisa acadêmica. Propomos as seguintes indagações: Como lidamos com a imaginação e com metáforas nas narrativas orais de histórias de vida? Como atendemos à demanda pela “verdade” em textos que ativam a subjetividade? Memórias individuais e subjetivas conferem cientificidade às narrativas? Situamos o problema da verdade, suas relações com a linguagem e com o conhecimento a partir de Friedrich Nietzsche e Mikhail Bakhtin. Articulamos revisão teórica e estudo de caso, considerando imagens mentais como mídias veiculadoras de memórias e, por isso mesmo, campo de estudos para a Comunicação e a História

Anagrelide platelet-lowering effect is due to inhibition of both megakaryocyte maturation and proplatelet formation: Insight into potential mechanisms

Background and Objectives: Anagrelide represents a treatment option for essential thrombocythemia patients. It lowers platelet counts through inhibition of megakaryocyte maturation and polyploidization, although the basis for this effect remains unclear. Based on its rapid onset of action, we assessed whether, besides blocking megakaryopoiesis, anagrelide represses proplatelet formation (PPF) and aimed to clarify the underlying mechanisms. Methods and Results: Exposure of cord blood-derived megakaryocytes to anagrelide during late stages of culture led to a dose- and time-dependent inhibition of PPF and reduced proplatelet complexity, which were independent of the anagrelide-induced effect on megakaryocyte maturation. Whereas anagrelide was shown to phosphorylate cAMP-substrate VASP, two pharmacologic inhibitors of the cAMP pathway were completely unable to revert anagrelide-induced repression in megakaryopoiesis and PPF, suggesting these effects are unrelated to its ability to inhibit phosphodiesterase (PDE) 3. The reduction in thrombopoiesis was not the result of down-regulation of transcription factors which coordinate PPF, while the myosin pathway was identified as a candidate target, as anagrelide was shown to phosphorylate the myosin light chain and the PPF phenotype was partially rescued after inhibition of myosin activity with blebbistatin. Conclusions: The platelet-lowering effect of anagrelide results from impaired megakaryocyte maturation and reduced PPF, both of which are deregulated in essential thrombocythemia. These effects seem unrelated to PDE3 inhibition, which is responsible for anagrelide′s cardiovascular side-effects and antiplatelet activity. Further work in this field may lead to the potential development of drugs to treat thrombocytosis in myeloproliferative disorders with an improved pharmacologic profile.Fil: Espasandin, Yesica Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Grodzielski, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Inteligência de negócios ou ciência de dados? O que dados bibliográficos inicialmente nos dizem?

A constante evolução tecnológica tem permitido que se gerem dados com maior volume, variedade e velocidade. Esse contexto pode gerar dúvidas sobre se continuará o modelo tradicional de business intelligence o qual se adequará à essa nova realidade, ou se se imporá a chamada datascience e suas novas e complementares formas de análise de dados. De forma a lançar luz sobre a relação entre essas duas áreas, no âmbito acadêmico, objetivou-se identificar se há relação na produção acadêmica da área de business intelligence e data science, considerando características de artigos das respectivas áreas. Analisou-se, com base em uma pesquisa bibliográfica que considerou artigos de periódicos publicados na base de dados Scopus, se haveria alguma forma de sobreposição das duas áreas, considerando  as seguintes características bibliográficas: autores, palavras-chave e citações. Com isso foi possível constatar uma tênue sobreposição entre os trabalhos das áreas estudadas e apontar questões para estudos futuros

Increased levels of plasma interleukin-6 soluble receptor in patients with essential thrombocythemia

Background and Objectives. The pathogenesis of essential thrombocythemia (ET), a disease characterized by megakaryocyte hyperplasia and persistent thrombocytosis, is not completely clarified. Interleukin-6 (IL-6), one of the cytokines related to megakaryocytic development, exerts its effect through binding to a cell surface receptor, IL-6Ra, and a signal transducing unit, gp130. Interestingly, the soluble form of the IL-6Ra, IL-6sR, is an agonist for IL-6 activity. In order to evaluate the possible participation of IL-6sR in ET we measured its levels in plasma, platelets and in the supernatant of a mononuclear cell culture. We also evaluated IL-6R on leukocyte membrane and IL-6R/IL-6sR mRNA expression in mononuclear cells. Design and Methods. Fifty-five patients with ET were evaluated. IL-6sR and IL-6 were measured by an ELISA technique. Mononuclear cells were cultured for 48 hr and IL-6sR released into the supernatant was measured. IL-6R on leukocyte surfaces was evaluated by flow cytometry. IL-6R and IL-6sR mRNA levels were assessed by semi-quantitative reverse transcription polymerase chain reaction. Results. Plasma IL-6sR levels were increased while intraplatelet levels were low in untreated ET patients. Plasma levels decreased during treatment. Non-stimulated mononuclear cells from ET patients released greater amounts of IL-6sR than did cells from normal controls in 48-hour culture. No abnormality was found in IL-6R or IL-6sR mRNA expression by mononuclear ET cells. IL-6R on leukocyte surfaces was normal. Interpretations and Conclusions. Increased plasma IL-6sR levels might have a role in the abnormal megakaryocytic proliferation seen in ET patients, while platelets and mononuclear cells could be the source of the above-mentioned high levels of plasma IL6sR.Fil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Kornblihtt, Laura Inés. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Vassallu, Patricia. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Glembotski, Ana. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Increased levels of plasma interleukin-6 soluble receptor in patients with essential thrombocythemia

Background and Objectives. The pathogenesis of essential thrombocythemia (ET), a disease characterized by megakaryocyte hyperplasia and persistent thrombocytosis, is not completely clarified. Interleukin-6 (IL-6), one of the cytokines related to megakaryocytic development, exerts its effect through binding to a cell surface receptor, IL-6Ra, and a signal transducing unit, gp130. Interestingly, the soluble form of the IL-6Ra, IL-6sR, is an agonist for IL-6 activity. In order to evaluate the possible participation of IL-6sR in ET we measured its levels in plasma, platelets and in the supernatant of a mononuclear cell culture. We also evaluated IL-6R on leukocyte membrane and IL-6R/IL-6sR mRNA expression in mononuclear cells. Design and Methods. Fifty-five patients with ET were evaluated. IL-6sR and IL-6 were measured by an ELISA technique. Mononuclear cells were cultured for 48 hr and IL-6sR released into the supernatant was measured. IL-6R on leukocyte surfaces was evaluated by flow cytometry. IL-6R and IL-6sR mRNA levels were assessed by semi-quantitative reverse transcription polymerase chain reaction. Results. Plasma IL-6sR levels were increased while intraplatelet levels were low in untreated ET patients. Plasma levels decreased during treatment. Non-stimulated mononuclear cells from ET patients released greater amounts of IL-6sR than did cells from normal controls in 48-hour culture. No abnormality was found in IL-6R or IL-6sR mRNA expression by mononuclear ET cells. IL-6R on leukocyte surfaces was normal. Interpretations and Conclusions. Increased plasma IL-6sR levels might have a role in the abnormal megakaryocytic proliferation seen in ET patients, while platelets and mononuclear cells could be the source of the above-mentioned high levels of plasma IL6sR.Fil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lev, Paola Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Kornblihtt, Laura Inés. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Vassallu, Patricia. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Glembotski, Ana. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin