Increased leukotriene C4 production in chronic myelogenous leukemia

The production of leukotrienes (LT) in peripheral blood leukocyte preparations from 9 patients with chronic myelogenous leukemia (CML) and 9 healthy controls was studied. Leukotriene generation was stimulated by the calcium ionophore A 23187 (1 mumol). Lipoxygenase products were separated and identified using a high performance liquid chromatography (HPLC) technique and computerized spectrophotometry. Leukotriene C4 (LTC4) was formed in significantly larger amounts by cells from the CML patients than cells from the controls; 14.4 +/- 4.3 pmol per 10(6) nucleated cells (mean +/- SE) and 4.0 +/- 1.2 pmol respectively (p less than 0.05). Seven of the 9 patients but none of the controls synthesized equal or higher amounts of LTC4 than LTB4. A highly significant difference in mean values of LTC4/(LTB4 + 20-OH-LTB4) ratios was observed; CML 0.69 +/- 0.08 versus controls 0.12 +/- 0.02, p less than 0.001. These findings suggest an increased LTC4 synthase activity in CML cells. In earlier studies we have found a decreased 12-lipoxygenase activity in CML bone marrow cells.