Increased Leukotriene C4 Production in Chronic Myelogenous Leukemia

Abstract

Abstract

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; 14.44.3 pmol per 10⁶ nucleated cells (meanSE) and 4.01.2 pmol respectively (p < 5.05). 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 0.690.08 versus controls 0.120.02, p < 5.001. 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.