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Review
. 2014 Oct 30;124(18):2784-92.
doi: 10.1182/blood-2014-04-526301. Epub 2014 Sep 18.

Marrow failure: a window into ribosome biology

Davide Ruggero  1 , Akiko Shimamura  2
Affiliations
Review

Marrow failure: a window into ribosome biology

Davide Ruggero et al. Blood. .

Abstract (V体育安卓版)

Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita are inherited syndromes characterized by marrow failure, congenital anomalies, and cancer predisposition. Genetic and molecular studies have uncovered distinct abnormalities in ribosome biogenesis underlying each of these 3 disorders. How defects in ribosomes, the essential organelles required for protein biosynthesis in all cells, cause tissue-specific abnormalities in human disease remains a question of fundamental scientific and medical importance. Here we review the overlapping and distinct clinical features of these 3 syndromes and discuss current knowledge regarding the ribosomal pathways disrupted in each of these disorders. We also explore the increasing complexity of ribosome biology and how this informs our understanding of developmental biology and human disease VSports手机版. .

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Figures

Figure 1
Figure 1
Overlapping and distinct clinical features of inherited marrow failure ribosomopathies. DBA, SDS, and DC are all characterized by marrow failure, predisposition to MDS/AML, and congenital anomalies. The primary feature of marrow failure in DBA is red-cell aplasia, although other hematologic lineages may also be variably affected. Although neutropenia is the most common feature of marrow failure in SDS, all 3 lineages may be depressed. Cellular and humoral immunologic abnormalities have been reported in DC and SDS. The spectrum of physical anomalies in these 3 syndromes shares both overlapping and distinct features. Exocrine pancreatic lipomatosis is characteristic of SDS, whereas pulmonary fibrosis is a common characteristic of DC. The risk of soft tissue sarcomas is increased in DBA, and the risk of squamous cell carcinomas of the oropharynx and gastrointestinal tract is elevated in DC. Data are insufficient to determine whether solid tumor risk is elevated in SDS. More detailed descriptions of clinical phenotypes have been reviewed.
Figure 2
Figure 2
Mutations of key ribosome components underlying ribosomopathies. The DKC1 gene encoding dyskerin (rRNA pseudouridine synthase) is frequently mutated in X-DC. The SBDS gene encodes the SDBS protein and is found to be mutated in SDS. RP genes encoding ribosomal proteins belonging to both the large and small ribosomal subunits are found to be mutated in DBA.
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References

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