Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target

• Published in: Blood Vol. 119; no. 15; pp. 3595 - 3603
• Main Authors: Pascale, Silvia, Petrucci, Giovanna, Dragani, Alfredo, Habib, Aida, Zaccardi, Francesco, Pagliaccia, Francesca, Pocaterra, Davide, Ragazzoni, Enzo, Rolandi, Giancarlo, Rocca, Bianca, Patrono, Carlo
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 12.04.2012; Americain Society of Hematology
• Subjects: Acceleration; Adult; Aged; Algorithms; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Aspirin - administration & dosage; Aspirin - therapeutic use; Biological and medical sciences; Cross-Over Studies; Cross-Sectional Studies - statistics & numerical data; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Drug Resistance - drug effects; Female; Half-Life; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Metabolic Networks and Pathways - drug effects; Middle Aged; Molecular Targeted Therapy - methods; Protein Biosynthesis - drug effects; Thrombocythemia, Essential - drug therapy; Thrombocythemia, Essential - metabolism; Thromboxane A2 - biosynthesis; Thromboxane A2 - pharmacokinetics; Prostaglandin-endoperoxide synthase; Hematology; Enzyme; Arachidonic acid derivatives; Enzyme inhibitor; Malignant hemopathy; Biosynthesis; Acetylsalicylic acid; Antiplatelet agent; Myeloproliferative syndrome; Essential thrombocythemia; Eicosanoid; Targeted drug; Oxidoreductases; Salicylates; Thromboxane; Cancer

Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A2 (TXA2) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive...