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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1582-1592. Prepublished online as a Blood First Edition Paper on June 5, 2008; DOI 10.1182/blood-2008-02-140012. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-02-140012v1 112/5/1582    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 Farrar, J. E. Articles by Arceci, R. J. Search for Related Content PubMed PubMed Citation Articles by Farrar, J. E. Articles by Arceci, R. J. Related Collections Hematopoiesis and Stem Cells Red Cells Plenary Papers Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia Jason E. Farrar1, Michelle Nater1, Emi Caywood1, Michael A. McDevitt2, Jeanne Kowalski3, Clifford M. Takemoto4, C. Conover Talbot, Jr5, Paul Meltzer6, Diane Esposito7, Alan H. Beggs8,9, Hal E. Schneider8, Agnieszka Grabowska8, Sarah E. Ball10, Edyta Niewiadomska11, Colin A. Sieff9,12,13, Adrianna Vlachos14, Eva Atsidaftos14, Steven R. Ellis15, Jeffrey M. Lipton14, Hanna T. Gazda8,9, and Robert J. Arceci1 1 Division of Pediatric Oncology, Department of Oncology, Kimmel Comprehensive Cancer Center, 2 Division of Hematology, Department of Medicine, 3 Division of Oncology Biostatistics, Department of Oncology, Kimmel Comprehensive Cancer Center, 4 Division of Pediatric Hematology, Department of Pediatrics, and 5 Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 6 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; 7 Cold Spring Harbor Laboratory, NY; 8 Division of Genetics and Program in Genomics, Children's Hospital Boston, MA; 9 Harvard Medical School, Boston, MA; 10 Department of Cellular and Molecular Medicine, St George's University of London, London, United Kingdom; 11 Department of Paediatric Haematology/Oncology, University Medical School, Warsaw, Poland; 12 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA; 13 Division of Pediatric Hematology, Children's Hospital Boston, MA; 14 Division of Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital, New Hyde Park, NY; Feinstein Institute for Medical Research, Manhasset, NY; and 15 Department of Biochemistry and Molecular Biology, University of Louisville, KY Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, congenital abnormalities, and cancer predisposition. Small ribosomal subunit genes RPS19, RPS24, and RPS17 are mutated in approximately one-third of patients. We used a candidate gene strategy combining high-resolution genomic mapping and gene expression microarray in the analysis of 2 DBA patients with chromosome 3q deletions to identify RPL35A as a potential DBA gene. Sequence analysis of a cohort of DBA probands confirmed involvement RPL35A in DBA. shRNA inhibition shows that Rpl35a is essential for maturation of 28S and 5.8S rRNAs, 60S subunit biogenesis, normal proliferation, and cell survival. Analysis of pre-rRNA processing in primary DBA lymphoblastoid cell lines demonstrated similar alterations of large ribosomal subunit rRNA in both RPL35A-mutated and some RPL35A wild-type patients, suggesting additional large ribosomal subunit gene defects are likely present in some cases of DBA. These data demonstrate that alterations of large ribosomal subunit proteins cause DBA and support the hypothesis that DBA is primarily the result of altered ribosomal function. The results also establish that haploinsufficiency of large ribosomal subunit proteins contributes to bone marrow failure and potentially cancer predisposition. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Diamond-Blackfan anemia: a new facet Akiko Shimamura Blood 2008 112: 1552-1553. [Full Text] [PDF] This article has been cited by other articles: M. Barkic, S. Crnomarkovic, K. Grabusic, I. Bogetic, L. Panic, S. Tamarut, M. Cokaric, I. Jeric, S. Vidak, and S. Volarevic The p53 Tumor Suppressor Causes Congenital Malformations in Rpl24-Deficient Mice and Promotes Their Survival Mol. Cell. Biol., May 15, 2009; 29(10): 2489 - 2504. [Abstract] [Full Text] [PDF] I. Dianzani and F. Loreni Diamond-Blackfan anemia: a ribosomal puzzle Haematologica, November 1, 2008; 93(11): 1601 - 1604. [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]

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