thromboxane-b2 and Leukemia--Myeloid--Acute

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Disseminated Intravascular Coagulation; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thromboxane B2

The appearance of the arachidonic acid metabolic pathway in human promyelocytic leukemia (HL-60) cells was investigated during 1 alpha,25-dihydroxyvitamin D-3-induced monocytic differentiation. 1 alpha,25-Dihydroxyvitamin D-3-treated HL-60 cells acquired the ability to convert [1-14C]arachidonic acid to thromboxane B2 and prostaglandin E2 during monocytic differentiation. The major cyclooxygenase product synthesized by the HL-60 cells after 3-4 days exposure to 1 alpha,25- dihydroxyvitamin D-3 (48 nM) was thromboxane B2 and its production was about 19-25-times higher than that of untreated HL-60 cells. The percent conversion of thromboxane B2 from [1-14C]arachidonic acid in the 1 alpha,25-dihydroxyvitamin D-3 (48 nM, 3 day exposure)-treated HL-60 cells was about 4.4% as compared to that (about 0.3%) of the untreated cells, whereas the percent conversion of thromboxane B2 from [1-14C]prostaglandin H2 in the 1 alpha,25-dihydroxyvitamin D-3-treated cell homogenate was about 22.4% as compared to that (about 13.6%) of the untreated cell homogenate. The stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on thromboxane B2 production from [1-14C]arachidonic acid and from [1-14C]prostaglandin H2 in HL-60 cells was inhibited by the addition of cycloheximide (1 microgram/ml). However, 1 alpha,25-dihydroxyvitamin D-3 (48 nM) did not significantly stimulate the arachidonic acid release either in HL-60 cells or in 1 alpha,25-dihydroxyvitamin D-3-induced cells. These results suggest that the stimulatory effect of 1 alpha,25-dihydroxyvitamin D-3 on the thromboxane production in HL-60 cells was not due to the activation of phospholipase A2 but due to the induction of fatty acid cyclooxygenase and thromboxane synthetase activities. Thromboxane A2 actively produced during the monocytic differentiation of HL-60 cells could influence the cell adhesiveness of the monocyte-macrophage-differentiated cells.

Topics: Arachidonic Acid; Arachidonic Acids; Calcitriol; Carbon Radioisotopes; Cell Differentiation; Cell Line; Cycloheximide; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Humans; Leukemia, Myeloid, Acute; Methacrylates; Monocytes; Prostaglandin Endoperoxides, Synthetic; Prostaglandin H2; Prostaglandins H; Thromboxane B2; Time Factors; Tretinoin

In a study of platelets from 13 patients with acute myeloid leukaemia abnormal aggregation and release reactions were found. A previously unrecognised quantitative defect of thromboxane B2 production may, at least in part, explain these findings. In contrast to a previous report, we were unable to show a convincing storage pool defect in these platelets. The platelet membrane glycoproteins were largely normal.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adolescent; Adult; Aged; Blood Platelets; Female; Glycoproteins; Humans; Leukemia, Myeloid, Acute; Male; Membrane Proteins; Middle Aged; Platelet Aggregation; Platelet Count; Serotonin; Thromboxane B2