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A new congenital dysmegakaryopoietic thrombocytopenia (Paris-Trousseau)
associated with giant platelet alpha-granules and chromosome 11 deletion at
11q23 [see comments]
J Breton-Gorius, R Favier, J Guichard, D Cherif, R Berger, N Debili, W Vainchenker and L Douay
INSERM U.91, Hopital Henri Mondor, Creteil, France.
This study characterizes a new congenital thrombocytopenia with mild
hemorrhagic tendency occurring in a woman and her child with the following
features. We found a deletion of the distal part of one chromosome 11
[del(11)q23.3-->qter] that was detected by cytogenetic analysis and
confirmed by chromosome painting in the two patients and also an increased
number of bone marrow megakaryocytes (MKs), including numerous
micromegakaryocytes (mMKs) associated with a normal platelet life span. A
normal number of MK colonies in culture was observed with one third of them
containing a few large MKs; however, these were always associated with mMKs
identified by immunologic staining. A massive cell lysis was observed at
the end of the maturation. Fifteen percent of the platelets in the
peripheral blood showed giant alpha- granules resulting from the fusion of
alpha-granules. These giant granules, which appeared in red on giemsa
stain, had a mean diameter of 1.5 microns and showed all markers (detected
at electron microscopy by immunogold method) of matrix and alpha-granule
membrane, ie, von Willebrand factor, fibrinogen, CD41, CD62P (P-selectin);
however, they differed from lysosomes because acid phosphatases were not
present. These giant alpha-granules were unable to release their contents
after stimulation by thrombin, in contrast to platelets with normal
morphology. Abnormalities in bone marrow MK maturation that were detected
at the electron microscopic level and that led to lysis of numerous MKs
were responsible for thrombocytopenia and were similar in both patients. MK
abnormalities are probably the consequence of the chromosome aberration.
ETS 1 and FLI, two proto-oncogenes that appear to be essential with GATA1
for the normal expression of MK-specific genes, map to 11q23-q24 and are,
thus, deleted in this thrombocytopenia. In conclusion, the association of
all these abnormalities constitutes a new familial platelet disorder and
may present a valuable model for exploring the role of some genes involved
in the regulation of thrombopoiesis.
Volume 85,
Issue 7,
pp. 1805-1814,
04/01/1995
Copyright © 1995 by The American Society of Hematology
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