A NEW CONGENITAL DYSMEGAKARYOPOIETIC THROMBOCYTOPENIA (PARIS-TROUSSEAU) ASSOCIATED WITH GIANT PLATELET ALPHA-GRANULES AND CHROMOSOME-11 DELETION AT 11Q23
A NEW CONGENITAL DYSMEGAKARYOPOIETIC THROMBOCYTOPENIA (PARIS-TROUSSEAU) ASSOCIATED WITH GIANT PLATELET ALPHA-GRANULES AND CHROMOSOME-11 DELETION AT 11Q23
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DOI：
10.1182/blood.v85.7.1805.bloodjournal8571805
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发表时间：
1995-04-01
期刊：
影响因子：
20.3
通讯作者：
DOUAY, L
中科院分区：
文献类型：
--
作者：
BRETONGORIUS, J;FAVIER, R;DOUAY, L
本研究的特点是一个新的先天性血小板减少症与轻度出血倾向发生在妇女和她的孩子与以下特点。我们发现一条染色体11 [de1(11)923.3—> qter]的远端部分缺失，这是通过细胞遗传学分析检测到的，并通过染色体涂画在两名患者中得到证实，同时骨髓巨核细胞（mk）数量增加，包括许多与正常血小板寿命相关的微巨核细胞（mMKs）。在培养中观察到正常数量的MK菌落，其中三分之一含有几个大MK；然而，这些总是与免疫染色鉴定的mmk相关。成熟结束时观察到大量细胞裂解。外周血中15%的血小板显示由α -颗粒融合产生的巨大α -颗粒。这些巨大的颗粒在giemsa染色上呈红色，平均直径为1.5 μ m，显示了基质和α颗粒膜的所有标记物，即血管性血液病因子、纤维蛋白原、CD41、CD62P （p -选择素）；然而，它们与溶酶体不同，因为不存在酸性磷酸酶。与正常形态的血小板不同，这些巨大的α颗粒在凝血酶的刺激下不能释放其内容物。在电镜水平上检测到骨髓MK成熟异常，导致大量MK溶解，这是导致血小板减少症的原因，在两例患者中是相似的。MK异常可能是染色体畸变的结果。ETS 1和FLI这两个原癌基因似乎是GATA1正常表达mk特异性基因所必需的，它们定位于11q23-q24，因此在这种血小板减少症中被删除。总之，所有这些异常的关联构成了一种新的家族性血小板疾病，并可能为探索一些参与血小板生成调节的基因的作用提供了一个有价值的模型。(C) 1995年由美国血液病学会出版。
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 [de1(11)923.3 --> 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 mu m 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. (C) 1995 by The American Society of Hematology.