Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia
Author's Manuscript 2011 February 1.
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2012
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| Online Access: | http://hdl.handle.net/1721.1/74158 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1811080339552993280 |
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| author | Sieff, Colin A. Yang, Jing Merida-Long, Lilia B. Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Sieff, Colin A. Yang, Jing Merida-Long, Lilia B. Lodish, Harvey F |
| author_sort | Sieff, Colin A. |
| collection | MIT |
| description | Author's Manuscript 2011 February 1. |
| first_indexed | 2024-09-23T11:29:46Z |
| format | Article |
| id | mit-1721.1/74158 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:29:46Z |
| publishDate | 2012 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/741582022-10-01T04:00:47Z Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia Sieff, Colin A. Yang, Jing Merida-Long, Lilia B. Lodish, Harvey F Massachusetts Institute of Technology. Department of Biology Lodish, Harvey F. Author's Manuscript 2011 February 1. Diamond Blackfan anaemia (DBA) is a severe congenital failure of erythropoiesis. Despite mutations in one of several ribosome protein genes, including RPS19, the cause of the erythroid specificity is still a mystery. We hypothesized that, because the chromatin of late erythroid cells becomes condensed and transcriptionally inactive prior to enucleation, the rapidly proliferating immature cells require very high ribosome synthetic rates. RNA biogenesis was measured in primary mouse fetal liver erythroid progenitor cells; during the first 24 h, cell number increased three to fourfold while, remarkably, RNA content increased sixfold, suggesting an accumulation of an excess of ribosomes during early erythropoiesis. Retrovirus infected siRNA RPS19 knockdown cells showed reduced proliferation but normal differentiation, and cell cycle analysis showed a G1/S phase delay. p53 protein was increased in the knockdown cells, and the mRNA level for p21, a transcriptional target of p53, was increased. Furthermore, we show that RPS19 knockdown decreased MYB protein, and Kit mRNA was reduced, as was the amount of cell surface KIT protein. Thus, in this small hairpin RNA murine model of DBA, RPS19 insufficient erythroid cells may proliferate poorly because of p53-mediated cell cycle arrest, and also because of decreased expression of the key erythroid signalling protein KIT. National Institutes of Health (U.S.) (Grant PO1 HL 32262) Amgen Inc. 2012-10-19T17:39:05Z 2012-10-19T17:39:05Z 2009-12 2009-07 Article http://purl.org/eprint/type/JournalArticle 0007-1048 1365-2141 http://hdl.handle.net/1721.1/74158 Sieff, Colin A. et al. “Pathogenesis of the Erythroid Failure in Diamond Blackfan Anaemia.” British Journal of Haematology 148.4 (2010): 611–622. https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1111/j.1365-2141.2009.07993.x British Journal of Haematology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Sieff, Colin A. Yang, Jing Merida-Long, Lilia B. Lodish, Harvey F Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title | Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title_full | Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title_fullStr | Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title_full_unstemmed | Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title_short | Pathogenesis of the Erythroid Failure in Diamond Blackfan Anemia |
| title_sort | pathogenesis of the erythroid failure in diamond blackfan anemia |
| url | http://hdl.handle.net/1721.1/74158 https://orcid.org/0000-0002-7029-7415 |
| work_keys_str_mv | AT sieffcolina pathogenesisoftheerythroidfailureindiamondblackfananemia AT yangjing pathogenesisoftheerythroidfailureindiamondblackfananemia AT meridalongliliab pathogenesisoftheerythroidfailureindiamondblackfananemia AT lodishharveyf pathogenesisoftheerythroidfailureindiamondblackfananemia |