5-LOX, 12-LOX and 15-LOX in immature forms of human leukemic blasts.
Several reports have demonstrated an important role of leukotriene B(4) (LTB(4)) in the immune system. We investigated whether leukemic blasts from acute myeloid leukemic (AML) and acute lymphoid leukemic (ALL) patients produced LTB(4), 12- and 15-hydroxyeicosatetraenoic acids (12-HETE and 15-HETE) and whether these compounds affected blast proliferation and apoptosis. Leukemic blasts from AML M(0-2) 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 LTB(4) 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 A(2) suggesting that contaminating platelets accounted for the release of these compounds. No significant effect of LTB(4), 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 LTB(4). However, the three major lipoxygenase metabolites of arachidonic acid; i.e., LTB(4), 12-HETE or 15-HETE, had no evident effect on their growth and apoptosis. We may speculate that LTB(4)-derived blast cells might initiate, augment or prolong tissue inflammation and damages by affecting the marrow and blood cytokine network.
Vincent
Christelle
C
Université de Limoges, Centre National de la Recherche Scientifique, CNRS UMR 6101, Faculté de Médecine, 2 rue Dr. Marcland, 87025 Limoges, France.
Fiancette
Rémi
R
Donnard
Magali
M
Bordessoule
Dominique
D
Turlure
Pascal
P
Trimoreau
Franck
F
Denizot
Yves
Y
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001752:Blast Crisis / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; D012333:RNA, Messenger; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium