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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4620-4626. Prepublished online as a Blood First Edition Paper on March 8, 2005; DOI 10.1182/blood-2004-08-3313. This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: 2004-08-3313v1 105/12/4620    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ebert, B. L. Articles by Sieff, C. A. Search for Related Content PubMed PubMed Citation Articles by Ebert, B. L. Articles by Sieff, C. A. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Genomics Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray Benjamin L. Ebert, Michele M. Lee, Jennifer L. Pretz, Aravind Subramanian, Raymond Mak, Todd R. Golub, and Colin A. Sieff From the Departments of Medical Oncology and Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA. Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia, is a model disease for the study of erythroid differentiation but is poorly understood. RPS19 is the only gene yet to have been associated with DBA, but its relevance to erythroid differentiation is unclear. The molecular basis for the stimulation of erythropoiesis by glucocorticoids in patients with DBA has not been identified. We demonstrate that targeted degradation of the RPS19 transcript, through retroviral expression of short hairpin RNAs (shRNAs), blocks the proliferation and differentiation of erythroid progenitor cells in cultured human CD34+ cells. Treatment of RPS19-deficient cells with dexamethasone restores erythroid differentiation to normal levels. We investigated the molecular basis of pharmacologic therapies for DBA using oligonucleotide microarrays to survey gene expression in CD34+ cells treated with combinations of dexamethasone, erythropoietin, stem cell factor, and interleukin-3. Dexamethasone did not alter expression of RPS19 but activated a genetic program that includes a set of key hematopoietic regulatory genes. Genes specific to erythroid progenitor cells were up-regulated by dexamethasone, while genes specific to nonerythroid lineages were down-regulated. Deficiency of RPS19 therefore blocks proliferation of immature erythroid progenitor cells, and dexamethasone activates proliferation of the same cell population through mechanisms independent of RPS19. (Blood. 2005;105:4620-4626) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: RPS19: pleads guilty in DBA case? Laure Coulombel Blood 2005 105: 4549-4550. [Full Text] [PDF] This article has been cited by other articles: N. Danilova, K. M. Sakamoto, and S. Lin Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family Blood, December 15, 2008; 112(13): 5228 - 5237. [Abstract] [Full Text] [PDF] M. A. Rey, S. P. Duffy, J. K. Brown, J. A. Kennedy, J. E. Dick, Y. Dror, and C. S. Tailor Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis Haematologica, November 1, 2008; 93(11): 1617 - 1626. [Abstract] [Full Text] [PDF] S. Robledo, R. A. Idol, D. L. Crimmins, J. H. Ladenson, P. J. Mason, and M. Bessler The role of human ribosomal proteins in the maturation of rRNA and ribosome production RNA, September 1, 2008; 14(9): 1918 - 1929. [Abstract] [Full Text] [PDF] J. E. Farrar, M. Nater, E. Caywood, M. A. McDevitt, J. Kowalski, C. M. Takemoto, C. C. Talbot Jr, P. Meltzer, D. Esposito, A. H. Beggs, et al. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia Blood, September 1, 2008; 112(5): 1582 - 1592. [Abstract] [Full Text] [PDF] T. Pederson Ribosomal protein mutations in Diamond-Blackfan anemia: might they operate upstream from protein synthesis? FASEB J, November 1, 2007; 21(13): 3442 - 3445. [Abstract] [Full Text] [PDF] J. Flygare and S. Karlsson Diamond-Blackfan anemia: erythropoiesis lost in translation Blood, April 15, 2007; 109(8): 3152 - 3154. [Abstract] [Full Text] [PDF] V. Choesmel, D. Bacqueville, J. Rouquette, J. Noaillac-Depeyre, S. Fribourg, A. Cretien, T. Leblanc, G. Tchernia, L. Da Costa, and P.-E. Gleizes Impaired ribosome biogenesis in Diamond-Blackfan anemia Blood, February 1, 2007; 109(3): 1275 - 1283. [Abstract] [Full Text] [PDF] E. C. Attar and R. P. Hasserjian Case 14-2006 -- a 25-year-old woman with anemia and iron overload. N. Engl. J. Med., May 11, 2006; 354(19): 2047 - 2056. [Full Text] [PDF]

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