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Related Collections Hematopoiesis and Stem Cells Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2001, Vol. 97, No. 1, pp. 139-146 HEMATOPOIESIS c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia Matthias Ballmaier, Manuela Germeshausen, Harald Schulze, Klara Cherkaoui, Sabine Lang, Annika Gaudig, Stephanie Krukemeier, Martin Eilers, Gabriele Strauß, and Karl Welte From the Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Germany. Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disease presenting with isolated thrombocytopenia in infancy and developing into a pancytopenia in later childhood. Thrombopoietin (TPO) is the main regulator of thrombocytopoiesis and has also been demonstrated to be an important factor in early hematopoiesis. We analyzed 9 patients with CAMT for defects in TPO production and reactivity. We found high levels of TPO in the sera of all patients. However, platelets and hematopoietic progenitor cells of patients with CAMT did not show any reactivity to TPO, as measured by testing TPO-synergism to adenosine diphosphate in platelet activation or by megakaryocyte colony assays. Flow cytometric analysis revealed absent surface expression of the TPO receptor c-Mpl in 3 of 3 patients. Sequence analysis of the c-mpl gene revealed point mutations in 8 of 8 patients: We found frameshift or nonsense mutations that are predicted to result in a complete loss of c-Mpl function in 5 patients. Heterozygous or homozygous missense mutations predicted to lead to amino acid exchanges in the extracellular domain of the receptor were found in 3 other patients. The type of mutations correlated with the clinical course of the disease. We propose a defective c-Mpl expression due to c-mpl mutations as the cause for thrombocytopenia and progression into pancytopenia seen in patients with CAMT. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Screening for c-mpl mutations in patients with congenital amegakaryocytic thrombocytopenia identifies a polymorphism Sonja van den Oudenrijn, Masja de Haas, Albert E. G. Kr. von dem Borne, Matthias Ballmaier, Manuela Germeshausen, and Karl Welte Blood 2001 97: 3675-3676. [Full Text] [PDF] This article has been cited by other articles: D. J. Hilton, B. T. Kile, and W. S. Alexander Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia Blood, May 28, 2009; 113(22): 5599 - 5604. [Abstract] [Full Text] [PDF] B. J. Lannutti, A. Epp, J. Roy, J. Chen, and N. C. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020