Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Ribosomal protein S19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model of Diamond-Blackfan anemia.
Journal Formal name:Stem cells (Dayton, Ohio)
Abbreviation:Stem Cells
ISSN code:15494918/10665099
Domestic / ForeginForegin
Volume, Issue, Page 26(2),pp.323-9
Author and coauthor Miyake Koich, Utsugisawa Taiju, Flygare Johan, Kiefer Thomas, Hamaguchi Isao, Richter Johan, Karlsson Stefan
Authorship 2nd author
Publication date 2008/02
Summary Diamond-Blackfan anemia (DBA) is a congenital red-cell aplasia in which 25% of the patients have a mutation in the ribosomal protein (RP) S19 gene. It is not known how the RPS19 deficiency impairs erythropoiesis and proliferation of hematopoietic progenitors. To elucidate molecular mechanisms in RPS19-deficient DBA, we analyzed the effects of RPS19 deficiency on erythropoietin (EPO)-induced signal transduction, cell cycle, and apoptosis in RPS19-deficient TF-1 cells. We did not find any abnormality in EPO-induced signal transduction. However, RPS19-deficient TF-1 cells showed G0/G1 arrest (82% vs. 58%; p < .05) together with accumulation of p21 and p27. The fraction of apoptotic cells detected by Annexin V analysis also increased compared with control cells (13% vs. 3.1%; p < .05). Western blot analysis of apoptosis-related proteins showed that the level of bcl-2 and Bad was decreased and Bax was increased in RPS19-deficient TF-1 cells. Moreover, primary CD34-positive cells from DBA patients detected by Annexin V analysis also generated a higher number of apoptotic cells compared with normal CD34-positive cells during in vitro culture (38% vs. 8.9%; n = 5; p < .001). Finally, we show that although RPS19 silencing reduces EPO-induced development of erythroid progenitors expressing glycophorin A (GPA), RPS19 silencing in cells already expressing GPA does not affect GPA expression. These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA.
DOI 10.1634/stemcells.2007-0569
PMID 17962699