Platelet arachidonic acid metabolism and platelet function in ten patients with chronic myelogenous leukemia.
We have compared the pathways of arachidonic acid (C 20:4) metabolism in platelets from ten patients with Philadelphia chromosome-positive CML with those of seven normal subjects. Platelets were incubated with 3H-arachidonic acid, gel-filtered, and treated with thrombin (5 U/ml). The cyclooxygenase and lipoxygenase-derived products and free arachidonic acid released from the platelets were separated by high pressure liquid chromatography and their radioactivity determined. The total uptake of 3H-C 20:4 by platelets from CML patients did not differ from controls, but the release of radioactivity in response to thrombin was significantly lower (p < 0.01) in CML patients (32.3% +/- 4.9% of total radioactivity was released from control platelets; 19.0% +/- 7.4% from CML platelets). Both cyclooxygenase and lipoxygenase-derived products were reduced, but there was no specific pattern of abnormality. Although there was no direct correlation between either the WBC or platelet count and impairment of platelet C 20:4 metabolism, the platelets from three patients with accelerated disease released the lowest total amount of 3H-C 20:4 metabolites. In a single patient, studied before and after successful chemotherapy (hydroxyurea), severe abnormalities in platelet arachidonic acid metabolism returned to normal after treatment.
D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002904:Chromosomes, Human, 21-22 and Y / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects
D001095:Arachidonic Acids