Elevated white blood cell synthesis of leukotriene C4 in chronic myelogenous leukaemia but not in polycythaemia vera

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Abstract
Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukemia (CML: n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromotography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 .+-. 7.9 pmol/106 WBC, mean .+-. SEM) than WBC from the healthy donors (9.0 .+-. 1.8), P < 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the .DELTA.-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 .+-. 0.25 v. 0.37 .+-. 0.07 in the controls, P < 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed: r = 0.6.00, P < 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, poststudy survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTB4 producing capacity in CML.