A NEW CONGENITAL DYSMEGAKARYOPOIETIC THROMBOCYTOPENIA (PARIS-TROUSSEAU) ASSOCIATED WITH GIANT PLATELET ALPHA-GRANULES AND CHROMOSOME-11 DELETION AT 11Q23

This study characterizes a new congenital thrombocytopenia with mild h emorrhagic tendency occurring in a woman and her child with the follow ing features. We found a deletion of the distal part of one chromosome 11 [de1(11)923.3 --> qter] that was detected by cytogenetic analysis and confirmed by chromosome painting in the two patients and also an i ncreased number of bone marrow megakaryocytes (MKs), including numerou s micromegakaryocytes (mMKs) associated with a normal platelet life sp an. A normal number of MK colonies in culture was observed with one th ird of them containing a few large MKs; however, these were always ass ociated with mMKs identified by immunologic staining. A massive cell l ysis was observed at the end of the maturation. Fifteen percent of the platelets in the peripheral blood showed giant alpha-granules resulti ng from the fusion of alpha-granules. These giant granules, which appe ared in red on giemsa stain, had a mean diameter of 1.5 mu m and showe d all markers (detected at electron microscopy by immunogold method) o f matrix and alpha-granule membrane, ie, von Willebrand factor, fibrin ogen, 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 l evel and that led to lysis of numerous MKs were responsible for thromb ocytopenia and were similar in both patients. MK abnormalities are pro bably 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, dele ted in this thrombocytopenia. In conclusion, the association of all th ese abnormalities constitutes a new familial platelet disorder and may present a valuable model for exploring the role of some genes involve d in the regulation of thrombopoiesis. (C) 1995 by The American Societ y of Hematology.