WASP is involved in proliferation and differentiation of human haemopoietic progenitors in vitro

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder charac terized by thrombocytopenia, immunodeficiency and eczema. X-linked thromboc ytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both p henotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (W ASP) gene. In this study we investigated the role of WASP in the differenti ation of CD34-positive (CD34(+)) cells isolated from the bone marrow of pat ients with WAS (n = 5) or with XLT (n = 4), Megakaryocyte colony formation was significantly decreased in patients with WAS when compared with normal controls. The formation of granulocyte-macrophage colonies and erythroid bu rsts were also decreased in WAS patinets. In contrast, in XLT patients, for mation of all these colonies was normal. However, in vitro proplatelet form ation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryo cytes obtained from WAS or XLT patients grown in vitro had abnormal morphol ogic features, which seemed to be caused by defective actin cytoskeletal or ganization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the alpha-granules and demarcation mem brane system. These observations indicate that WASP is involved in the prol iferation and differentiation of CD34(+) haemopoietic progenitor cells prob ably by its participation in signal transduction and in the regulation of t he cytoskeleton.