title: Qualitative platelet 12-lipoxygenase abnormality in a patient with essential thrombocythemia.
abstract: Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been reported in some patients with myeloproliferative disorders (MPD). We report here for the first time a novel qualitative abnormality of the 12-LOX enzyme of platelets from a patient with essential thrombocythemia. The anti-12-LOX immunoprecipitates from the patient's platelet homogenates showed a deficiency of 12-LOX activity, but contained normal amount of 12-LOX protein. There was no difference in subcellular localization of the enzyme between the patient's platelets and normal ones. This 12-LOX protein lacking its enzyme activity showed slightly larger electrophoretic mobility than normal one, suggesting a molecular abnormality of the enzyme. However, we could not detect any genetic mutation causing such abnormalities in all exons of 12-LOX gene by sequencing the patient's PCR-amplified DNA. Thus, our results indicate that the deficient activity of this abnormal 12-LOX protein is probably due to a posttranslational modification, and the possibility that platelets of some MPD patients have qualitative abnormality of the 12-LOX enzyme besides quantitative ones.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tomo
authors.forename: H
authors.initials: H
authors.lastname: Takayama
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: J
authors.initials: J
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Okuma
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood* / Q000172:deficiency; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology; D011087:Polycythemia Vera / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational; D013920:Thrombocythemia, Essential / Q000201:enzymology*
chemical_list: D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase