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Vol. 42. Issue S2.
Pages 119-120 (November 2020)
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Vol. 42. Issue S2.
Pages 119-120 (November 2020)
200
Open Access
DEREGULATION OF BONE MARROW EICOSANOIDS IN ESSENTIAL THROMBOCYTHEMIA AND PRIMARY MYELOFIBROSIS PATIENTS
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J.G. Cominala,b, M.C. Cacemiroa,b, C.A. Sorgia, L.H. Facciolia, L.L. Figueiredo-Pontesb,c, F.A. Castroa,b
a Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
b Fundação Hemocentro de Ribeirão Preto (FUNDHERP), Ribeirão Preto, SP, Brazil
c Departamento de Imagens Médicas, Hematologia e Oncologia Clínica, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
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Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are clonal disease classified as myeloproliferative neoplasms. These diseases exhibits hyperproliferation of megacaryocyte lineage, apoptosis resistance, oncoinflammation, hematopoesis deregulation and hematopoietic stem cell niche modifications, including bone marrow fibrosis. Eicosanoids are a group of bioactive lipids derived from 20-carbon polyunsaturated essential fatty acids which can act as signaling molecules modulating the regulation of hematopoesis. Eicosanoids can also contribute to carcionogenesis and chronic inflammation. Aims: to evaluate eicosanoids levels in bone marrow plasma from healthy individuals (HI), ET and PMF patients. To determine eicosanoids profiles of each group correlating with blood count parameters. Subjects and methods: Bone marrow plasma samples from 10 ET (median age = 56 years [31 – 77], 1 man and 7 women), 8 PMF (median age= 68.5 years [58-80], 5 men and 3 women) patients, and 8 HI (median age= 36.5 years [19-72], 4 men and 4 women) were enrolled in this study. Samples were collected at Ribeirão Preto Medical School Hospital (HC-FMRP-USP, Ribeirão Preto, Brazil). The study was approved by the Human Research Ethics Committee of the School of Pharmaceutical Sciences of Ribeirão Preto. Eicosanoids quantification and analysis of 8 mediators (AA, 5-HETE, 11-HETE, 12-HETE, 15-HETE, 15-OXO-ETE, EPA and TXB2) was perfomed by high performance liquid chromatography. Blood count parameters were obtain from the volunteers medical records which includes red blood cell count (RBC), white blood cell count (WBC), hemoglobin concentration (HB) and platelets count (PLT). Results: Higher levels of 5-HETE were demonstrated in ET (p = 0.0058) and PMF (p = 0.0141) patients compared to HI. Comparisons between diseases showed elevation of 15-HETE in ET compared to PMF patients (p = 0.0271), and decresed concentration of 12-HETE in ET compared PMF patients (p = 0.0500). Eicosanoids profile reveals disease-relevant mediators (>50% of group individuals categorized as high producers). Five mediators (5-HETE, 11-HETE, 12-HETE, 15-HETE and 15-OXO-ETE) were considered important in ET group, while in PMF group only AA was relevant. The HI group exhibits only low producers for analyzed mediators. The correlation analysis between eicosanoids levels and blood count parameters showed many positive correlation in PMF group, including 11-HETE and WBC (p = 0.0415, r = 0.6667) and PLT (p = 0.0322, r = 0.6946); 12-HETE and RBC (p = 0.0481, r = 0.6429), WBC (p = 0.0002, r = 0.9762) and PLT (p = 0.0086, r = 0.8264); 15-HETE and WBC (p = 0.0184, r = 0.7619) and PLT (p = 0.0065, r = 0.8383); EPA and HB (p = 0.0357, r = 0.7326); 15-OXO-ETE and RBC (p = 0.0147, r = 0.7785), WBC (p = 0.0351, r = 0.6826), HB (p = 0.0378, r = 0.6707) and PLT (p = 0.0086, r = 0.8193). The ET group exhibits only one positive correlation between 15-HETE and PLT (p = 0.0075, r = 0,7576). Conclusions: Our results demonstrated that ET and PMF patients show deregulation in eicosanoids biosynthesis. The eicosanoid profile differ among analyzed groups, and ET exhibits higher number of disease-relevant mediators. Taken together, these results suggest that eicosanoids are relevant for MPN and had the potential to contributes to some MPN pathogenesis as the oncoinflammation, hematopoesis deregulation and bone marrow fibrosis.

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Hematology, Transfusion and Cell Therapy

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