title: Ribosome defects in disorders of erythropoiesis.
abstract: Over the past decade, genetic lesions that cause ribosome dysfunction have been identified in both congenital and acquired human disorders. These discoveries have established a new category of disorders, known as ribosomopathies, in which the primary pathophysiology is related to impaired ribosome function. The protoptypical disorders are Diamond-Blackfan anemia, a congenital bone marrow failure syndrome, and the 5q- syndrome, a subtype of myelodysplastic syndrome. In both of these disorders, impaired ribosome function causes a severe macrocytic anemia. In this review, we will discuss the evidence that defects in ribosomal biogenesis cause the hematologic phenotype of Diamond-Blackfan anemia and the 5q- syndrome. We will also explore the potential mechanisms by which a ribosomal defect, which would be expected to have widespread consequences, may lead to specific defects in erythropoiesis.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Karp Research Building, CHRB 05.211, 1 Blackfan Circle, Boston, MA, 02115, USA.|Department of Medicine, Children's Hospital Boston, Boston, MA, 02115, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Narla
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Karp Research Building, CHRB 05.211, 1 Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Slater N
authors.initials: SN
authors.lastname: Hurst
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA. bebert@partners.org.|Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Karp Research Building, CHRB 05.211, 1 Blackfan Circle, Boston, MA, 02115, USA. bebert@partners.org.|Harvard Stem Cell Institute, Cambridge, MA, 02138, USA. bebert@partners.org.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics / Q000378:metabolism*; D029503:Anemia, Diamond-Blackfan / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D012269:Ribosomal Proteins