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

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.