QUALITATIVE PLATELET 12-LIPOXYGENASE ABNORMALITY IN A PATIENT WITH ESSENTIAL THROMBOCYTHEMIA

Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been rep orted in some patients with myeloproliferative disorders (MPD). We rep ort here for the first time a novel qualitative abnormality of the 12- LOX enzyme of platelets from a patient with essential thrombocy themia . The anti-12-LOX immunoprecipitates from the patient's platelet homog enates showed a deficiency of 12-LOX activity, but con rained normal a mount of 12-LOX protein. There was no difference in subcellular locali zation 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 abno rmality of the enzyme. However, we could not detect any genetic mutati on causing such abnormalities in all exons of 12-LOX gene by sequencin g 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 one.