title: WASP is involved in proliferation and differentiation of human haemopoietic progenitors in vitro.
abstract: The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study we investigated the role of WASP in the differentiation of CD34-positive (CD34+) cells isolated from the bone marrow of patients 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 bursts were also decreased in WAS patinets. In contrast, in XLT patients, formation of all these colonies was normal. However, in vitro proplatelet formation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryocytes obtained from WAS or XLT patients grown in vitro had abnormal morphologic features, which seemed to be caused by defective actin cytoskeletal organization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the alpha-granules and demarcation membrane system. These observations indicate that WASP is involved in the proliferation and differentiation of CD34+ haemopoietic progenitor cells probably by its participation in signal transduction and in the regulation of the cytoskeleton.
authors.affiliation: Department of Paediatrics, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kajiwara
authors.forename: S
authors.initials: S
authors.lastname: Nonoyama
authors.forename: M
authors.initials: M
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Morio
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: H
authors.initials: H
authors.lastname: Okawa
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: S
authors.initials: S
authors.lastname: Ohga
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Hibi
authors.forename: H
authors.initials: H
authors.lastname: Hashimito
authors.forename: A
authors.initials: A
authors.lastname: Shibuya
authors.forename: H D
authors.initials: HD
authors.lastname: Ochs
authors.forename: T
authors.initials: T
authors.lastname: Nakahata
authors.forename: J I
authors.initials: JI
authors.lastname: Yata
mesh_terms: D001792:Blood Platelets / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D019084:Fluorescent Antibody Technique, Indirect; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007223:Infant; D008533:Megakaryocytes / Q000648:ultrastructure; D008854:Microscopy, Electron; D011506:Proteins / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000473:pathology*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein