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

Abstract

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.

Keywords::

• Ribosomies
• p53 pathway
• Diamond–Blackfan anemia
• myelodysplastic syndrome
• hematologic malignancies

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was funded by the NIH (grants R01 HL082945 and P01 CA108631), the Leukemia and Lymphoma Society and the Burroughs-Wellcome Fund.