Deficient Lipoxin Synthesis: A Novel Platelet Dysfunction in Myeloproliferative Disorders With Special Reference to Blastic Crisis of Chronic Myelogenous Leukemia

• Published in: BLOOD Vol. 78; no. 11; pp. 2989 - 2995
• Main Authors: Stenke, Leif, Edenius, Charlotte, Samuelsson, Jan, Lindgren, Jan Åke
• Format: Journal Article Publication
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.1991; The Americain Society of Hematology
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Biological and medical sciences; Blast Crisis; Blood Platelets - metabolism; Fatty Acids, Unsaturated - metabolism; Hematologic and hematopoietic diseases; Humans; Hydroxyeicosatetraenoic Acids - biosynthesis; Hydroxyeicosatetraenoic Acids - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukotriene A4; Leukotrienes - metabolism; Lipoxins; Medical sciences; Myeloproliferative Disorders - metabolism; SRS-A - metabolism; Human; Myeloproliferative syndrome; Platelet; Synthesis; Arachidonic acid derivatives; Deficiency; Platelet function; Chronic myelocytic leukemia; Exploration; Malignant hemopathy; Blast transformation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V78.11.2989.2989

The capacity to convert exogenous leukotriene A4 to lipoxins (LXs) was investigated in platelet suspensions from patients with myeloproliferative disorders (MPD) (n = 22) and healthy control subjects (n = 14). Platelets isolated from the controls produced mainly LXA4, but also 6(S)-LXA4 and the all-trans isomers of lipoxins A4 and B4, as determined by high-performance liquid chromatography and computerized UV spectroscopy. In comparison to control levels, the mean LX synthesis was significantly lower in platelets from the MPD patients (438.7 ± 62.8 and 157.4 ± 31.2 pmol LXA4 per 109 platelets, respectively; mean ± SEM; P = .0001). Platelets from six of the patients showed a particularly low capacity to produce LXs, resulting in LX levels below the detection limit or less than 7% of mean control levels. Notably, all these patients were in blastic crisis of chronic myelogenous leukemia (CML). This severely deficient LX production was paralleled by a dramatically attenuated conversion of arachidonic acid to 12-HETE (12-hydroxyeicosatetraenoic acid), while the formation of HHT (12-hydroxyheptadecatrienoic acid), a product formed via the prostaglandin endoperoxide synthase pathway, was normal. In addition, longitudinal studies of CML patients showed that blastic metamorphosis was associated with a markedly reduced capability to synthesize LXs, while this capacity improved after retransformation into a second chronic phase. The results reveal deficient LX synthesis as a novel platelet dysfunction in MPD, particularly in blastic crisis of CML in which an essentially abolished 12-lipoxygenase activity may be a general phenomenon.