The emerging importance of ribosomal dysfunction in the pathogenesis of hematologic disorders

Leuk Lymphoma. 2014 Mar;55(3):491-500. doi: 10.3109/10428194.2013.812786. Epub 2013 Aug 28.


More than a decade has passed since the initial identification of ribosomal protein gene mutations in patients with Diamond-Blackfan anemia (DBA), a hematologic disorder that became the founding member of a class of diseases known as ribosomopathies. In these diseases, genetic abnormalities that result in defective ribosome biogenesis cause strikingly tissue-specific phenotypes in patients, specifically bone marrow failure, craniofacial abnormalities and skeletal defects. Several animal models and numerous in vitro studies have demonstrated that the p53 pathway is central to the ribosomopathy phenotype. Additionally, there is mounting evidence of a link between the dysregulation of components of the translational machinery and the pathology of various malignancies. The importance of the role of ribosomal dysfunction in the pathogenesis of hematologic disorders is becoming clearer, and elucidation of the underlying mechanisms could have broad implications for both basic cellular biology and clinical intervention strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hematologic Diseases / diagnosis
  • Hematologic Diseases / genetics*
  • Hematologic Diseases / metabolism*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / metabolism
  • Heme / metabolism
  • Hemoglobins / metabolism
  • Humans
  • Ribosomes / genetics*
  • Ribosomes / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Hemoglobins
  • Tumor Suppressor Protein p53
  • Heme