5-LOX, 12-LOX and 15-LOX in immature forms of human leukemic blasts

Abstract Several reports have demonstrated an important role of leukotriene B4 (LTB4 ) in the immune system. We investigated whether leukemic blasts from acute myeloid leukemic (AML) and acute lymphoid leukemic (ALL) patients produced LTB4 , 12- and 15-hydroxyeicosatetraenoic acids (12-HETE and 15-HETE) and whether these compounds affected blast proliferation and apoptosis. Leukemic blasts from AML M0-2 and ALL patients expressed 5-LOX, 12-LOX and 15-LOX transcripts. Quantitative polymerase chain reaction indicated that 5-LOX transcripts were far more abundant than 12-LOX and 15-LOX ones. Leukemic blasts expressed 5-LOX activating protein (FLAP) transcripts and produced LTB4 in response to calcium ionophore. In contrast no 15-HETE production was found. Calcium ionophore-stimulated leukemic blasts produced 12-HETE but also released thromboxane A2 suggesting that contaminating platelets accounted for the release of these compounds. No significant effect of LTB4 , 12-HETE or 15-HETE could be documented on leukemic blast growth and on their apoptose rate. Results of the present study indicate that immature form of leukemic blasts produce LTB4 . However, the three major lipoxygenase metabolites of arachidonic acid; i.e., LTB4 , 12-HETE or 15-HETE, had no evident effect on their growth and apoptosis. We may speculate that LTB4 -derived blast cells might initiate, augment or prolong tissue inflammation and damages by affecting the marrow and blood cytokine network.