Deficient lipoxin synthesis: a novel platelet dysfunction in
myeloproliferative disorders with special reference to blastic crisis of
chronic myelogenous leukemia
L Stenke, C Edenius, J Samuelsson and JA Lindgren
Department of Physiological Chemistry, Danderyd Hospital, Stockholm,
Sweden.
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
10(9) 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-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.
Volume 78,
Issue 11,
pp. 2989-2995,
12/01/1991
Copyright © 1991 by The American Society of Hematology
