info:eu-repo/semantics/article
Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia
Fecha
2009-01Registro en:
Salim, Juan Pablo; Goette, Nora Paula; Lev, Paola Roxana; Chazarreta, Carlos Daniel; Heller, Paula Graciela; et al.; Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia; Wiley Blackwell Publishing, Inc; British Journal of Haematology; 144; 1; 1-2009; 69-77
0007-1048
CONICET Digital
CONICET
Autor
Salim, Juan Pablo
Goette, Nora Paula
Lev, Paola Roxana
Chazarreta, Carlos Daniel
Heller, Paula Graciela
Alvarez, Clarisa Ester
Molinas, Felisa Concepción
Marta, Rosana Fernanda
Resumen
This study investigated the involvement of chemokines including stromal derived factor 1 (SDF-1), interleukin 8 (IL-8), growth-related oncogene alpha (GRO-a) and their receptors, CXCR4, CXCR2 and CXCR1 in essential thrombocythemia (ET), a chronic myeloproliferative disease characterized by megakaryocytic hyperplasia and high platelet count. Fifty-three ET patients were studied. Plasma levels of SDF-1, IL-8 and GRO-a, evaluated by enzymelinked immunosorbent assay, and flow cytometric analysis of CXCR1 and CXCR2 on the platelet membrane, were found to be normal in ET patients. CXCR4 expression on platelet surface aswell as platelet CXCR4mRNAdetected by real-time reverse transcription polymerase chain reaction, were decreased. Platelet CXCR4 internalization rate was normal while SDF-1-induced platelet aggregation was delayed, decreased or absent. Immunohistochemical staining revealed that megakaryocytes were also affected. CXCR4 decrease was not observed either in peripheral white blood cells or in circulating CD34+ precursors. These results show that CXCR4 is decreased in the megakaryocytic lineage in ET, mainly due to a reduced CXCR4 production, and an abnormal platelet response to SDF-1. This report is the first to describe platelet and megakaryocytic CXCR4 deficiency in a human disease and the presence of this abnormality in a megakaryocytic-related illness highlights the important role of SDF-1/CXCR4 axis in platelet development.