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Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients' peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients' transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN.

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BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype and JAK2 V617F in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944 and the JAK2 V617F, in which the G allele (OR 3.4; p < 0.0001) and GG genotype (OR 4.9; p = 0.0016) were associated with JAK2 V617F + and an increase in variant allele frequency (GG: OR 15.8; p = < 0.0001; G: OR 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F + _VAF ≥ 50%, and laboratory alterations in the erythroid lineage.

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INTRODUCTION: Considering the evolving diagnostic criteria of polycythemia vera (PV), we analyzed the utility of serum erythropoietin (EPO) as a predictive marker for differentiating polycythemia vera (PV) from other etiologies of erythrocytosis. PATIENTS AND METHODS: We conducted a retrospective study after a review of electronical medical records from January 2005 to December 2016 with diagnosis of erythrocytosis using International Classification of Disease-specific codes. To evaluate the diagnostic performance of EPO levels and JAK2-V617F mutation, we constructed a receiver-operated characteristic curve of sensitivity versus 1-specificity for serum EPO levels and JAK2-V617F mutation as predictive markers for differentiating PV from other causes of erythrocytosis. RESULTS: We surveyed 577 patients with erythrocytosis. Median patient age was 59.2 years, 57.72% (n = 329) were male, 86.3% (n = 491) were white, and only 3.3% (n = 19) were African American. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Therefore, the PV diagnostic methodology using JAK2-V617 is better than the EPO test. An EPO level of < 2 mIU/mL was > 99% specific to predict PV but was only 12% sensitive. CONCLUSION: In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.

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INTRODUCTION: Polycythemia vera (PV) is a disorder characterized by clonal proliferation of myeloid cells and increased red blood cell mass. Recently, the revised 2016 WHO classification of myeloid neoplasms decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new proposed cutoffs have remarkable overlap with the normal reference values reported and the clinical impact of these new cutoffs has not been widely assessed in the general population. METHODS: We retrospectively examined 248 839 patients with presumptively normal complete blood cell results, consecutively obtained in an outpatient setting. RESULTS: The proportion of men with Hb >165 g/L was 5.99%, Hct>49% was 2.4%, and Hb >165 g/dL or Hct>49% was 6.48%, while the proportion of women with Hb >160 g/L was 0.22%, Hct>48% was 0.11%, and Hb >160 g/L or Hct>48% was 0.28%. CONCLUSION: The isolated use of the proposed Hb/Hct levels as a definer of polycythemia may lead to a substantial increase in unnecessary diagnostic tests. In cases with borderline levels of hemoglobin, the diagnostic workup of PV should only be indicated in the presence of clinical and/or laboratorial features associated with MPN.

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Bleeding and thrombosis in myeloproliferative disorders (MPD) are common events, sometimes both are present in the same patient during the course of the disease. Platelet activation in patients with MPD is often suggested. The present study analyses the presence of circulating activated platelets, using simultaneously flow cytometry and aggregometric studies in MPD. We studied 28 patients: 13 with polycythaemia vera, seven with essential thrombocythaemia, and eight chronic myeloid leukaemia. We performed functional tests, aggregation and adenosine triphosphate (ATP) release and flow cytometric assays (mepacrine staining and platelet activation markers CD62, CD63 and fibrinogen binding (B-FG)). Twenty-one MPD samples (75%) had reduced aggregation and ATP release. Acquired delta-SPD was detected in 11 of 28 MPD patients (39%), and we found no association between reduced mepacrine labelling and abnormal ATP release. High levels of activation markers were obtained: CD62 in 19 of 28 patients (68%), CD63 in 13 of 28 patients (46%) and B-FG in 19 of 28 patients (68%). The most prevalent abnormality was a reduced aggregation and ATP release. The lack of association between ATP release and mepacrine labelling suggests that other mechanisms, besides the deficit of intraplatelet ATP/adenosine diphosphate, might occur. High levels of activation markers were also observed. We conclude that both tests are complementary and necessary to understand the functional status of platelets in MPD.

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Magnetic resonance (MR) imaging was performed in 14 patients with biopsy-proved polycythemia vera (n = 4) or myelofibrosis (n = 10) to determine whether MR imaging findings can be correlated with the clinicopathologic diagnosis and established clinical parameters of severity (serum lactate dehydrogenase [LDH] and cholesterol levels) and chronicity (spleen size). Evaluation of marrow in the proximal femurs showed that patients could be categorized into three distinct groups based on anatomic patterns of normal fatty and abnormal low-signal-intensity (non-fatty) marrow in the femoral capital epiphysis (FCE) and greater trochanter (GT). Patients with nonfatty marrow in both the FCE and GT (n = 8) had significantly higher serum LDH (P less than .02) and lower serum cholesterol (P less than .02) levels than patients with fatty marrow in at least the GT (n = 6). Splenic volume, as measured from MR images, was significantly greater in the myelofibrosis group than in the polycythemia vera group (P less than .001). MR imaging provided a better understanding of these hematologic disorders and novel parameters for classification that are different from conventional histologic and laboratory data.

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The theta globin gene is the most recently discovered member of the alpha globin gene family. Its pattern of expression during development is not fully defined, and its encoded protein has not yet been detected in vivo. The detection of theta globin messenger RNA (mRNA) in embryonic and fetal erythroid tissue but not in adults has suggested that theta is an embryonic globin gene. The present study further defines the pattern of theta globin gene expression. We use a modification of the highly sensitive polymerase chain reaction (PCR) technique to assess the levels of theta globin gene expression during development. We confirm the presence of the theta globin mRNA in embryonic and fetal erythroid tissue, and, in addition, we find theta mRNA in the peripheral reticulocytes of normal adults. Furthermore, using the same analytic approach, we detect low but significant levels of the embryonic zeta and epsilon mRNAs in reticulocytes of normal adults. Both zeta and theta gene expression appears erythroid specific in that neither mRNA species is detected in RNA isolated from brain tissue, peripheral blood mononuclear cells, or three nonerythroid cell lines (B-lymphocyte, T-lymphocyte, and hepatoma cell lines). The relative levels of zeta and theta gene expression were assayed during development by a coamplification technique. The results demonstrate the expected developmental regulation of zeta globin mRNA. In contrast, the level of theta globin mRNA fails to demonstrate the significant changes of the magnitude seen in other globin genes and remains low in embryonic, fetal, and adult life. The lack of zeta and epsilon globin proteins in normal adults using highly sensitive immunologic techniques, as reported by others, stands in contrast to these mRNA results and suggests a gap between mRNA and protein expression.

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Polycythemia vera is a stem cell disorder that results in an increase in the production of red blood cells. Although numerous mechanisms have been suggested, the cause of the disease is unknown. Diagnosis is based on clinical and laboratory presentation. This article reviews the history of polycythemia vera and illustrates a representative case report of the disease process. Postoperative morbidity in the surgical patient is discussed with respect to preoperative therapeutic control. Recommendations are made for preoperative therapy in patients undergoing oral and maxillofacial surgery.

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Periodical follow-up evaluations at intervals from 3 to 6 months of haematocrit, blood volume and ferrokinetic, during a 2.5 year period were performed in 18 polycythaemia vera (PV) patients to find the most characteristic parameters for the determination of the erythropoietic system functional activity. Our results suggest that in PV it is advisable to carry out further determination of red cell volume to determine exactly the degree of erythrocytosis. We found that plasma iron turnover (PIT) followed by 59Fe T1/2 are the first parameters to return to normal and the first to alter after a prolonged period of a normal ferrokinetic status. We suggest these may be used as the most reliable indicators for the haematological control of PV.

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Several platelet function abnormalities have been described in the myeloproliferative syndromes. We have measured the intraplatelet vWF:Ag and fibrinogen (FI) in the platelet lysates by Laurell technique in 11 patients with polycythemia vera (PV), 10 with essential thrombocythemia (ET), 14 with chronic myelocytic leukaemia (CML) and 3 with myelofibrosis (MF) and these results were correlated with platelet function abnormalities. Decreased intraplatelet levels of vWF:Ag and FI were found in all the patients with ET and MF, in 8 out of 11 PV and 3 out of 14 CML. A statistical significant correlation was observed between the intraplatelet levels of vWF:Ag and FI in the control group and in CML and PV, but no correlation was found in ET and MF. No correlation was observed between the plasmatic and the intraplatelet levels of vWF:Ag and FI in any group. Evidences of platelet activation (spontaneous platelet aggregation or circulating platelet aggregates) were observed in 40% of the cases with ET and PV, and all these cases had low intraplatelet levels of both antigens. None of the cases with MF had evidences of platelet activation and 2 out of 14 patients with CML had platelet activation. The deficiency of the dense bodies was less frequent than the depletion of the alpha granules (5 out of 11 PV, 4 out of 10 ET, 6 out of 14 CML and 2 out of 3 MF). The low intraplatelet contents of vWF: Ag and FI, more frequently observed in ET and PV, may be the result of platelet activation and in vivo release, but megakaryocyte dysfunction is more likely in myelofibrosis.

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La función plaquetaria fue estudiada en 18 pacientes con policitemia vera en diferentes estadios evolutivos. El 27,7 porciento de los casos presentaron episodios trombóticos y el 16,6 porciento hemorrágicos. El trastorno más frecuentemente encontrado fue la alteración de la agregación plaquetaria a la epinefrina. Se encontró algún efecto corrector de este trastorno con el tratamiento mielosupresor. No se observó una correlación significativa entre la disfución plaquetaria y la cifra de plaquetas, leucocitos, hemoglobina y hematócrito(AU)

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