Jeffrey M Lipton1, Steven R Ellis. 1. Elmezzi Graduate School of Molecular Medicine, The Feinstein Institute for Medical Research, USA. jlipton@lij.edu
Abstract
PURPOSE OF REVIEW: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid failure, congenital anomalies and predisposition to cancer. Recently, the notion of DBA as a disorder of ribosome biogenesis has been clarified. Correlations between molecular underpinnings and disease pathophysiology, while elusive, are beginning to emerge. Advances in these areas will be explored in this review. RECENT FINDINGS: All known genes mutated in DBA encode ribosomal proteins associated with either the small (RPS) or large (RPL) subunit and in these cases ribosomal protein haploinsufficiency gives rise to the disease. The number of genes affected, their potential interactions with the environment and modifier genes, and the myriad of potential signaling pathways linking abortive ribosome synthesis to cell-cycle regulators may all contribute to disease heterogeneity. Genotype/phenotype relationships emerging over the past year promise to shed light on these complex interrelationships and their role in DBA pathophysiology. SUMMARY: The nosology of DBA has recently expanded to include two distinct disease categories: a classical inherited bone marrow failure syndrome and a 'ribosomopathy'. The description of DBA as a ribosomopathy has provided a context for scientific inquiry analogous to the description of Fanconi anemia as a disorder of DNA repair.
PURPOSE OF REVIEW: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid failure, congenital anomalies and predisposition to cancer. Recently, the notion of DBA as a disorder of ribosome biogenesis has been clarified. Correlations between molecular underpinnings and disease pathophysiology, while elusive, are beginning to emerge. Advances in these areas will be explored in this review. RECENT FINDINGS: All known genes mutated in DBA encode ribosomal proteins associated with either the small (RPS) or large (RPL) subunit and in these cases ribosomal protein haploinsufficiency gives rise to the disease. The number of genes affected, their potential interactions with the environment and modifier genes, and the myriad of potential signaling pathways linking abortive ribosome synthesis to cell-cycle regulators may all contribute to disease heterogeneity. Genotype/phenotype relationships emerging over the past year promise to shed light on these complex interrelationships and their role in DBA pathophysiology. SUMMARY: The nosology of DBA has recently expanded to include two distinct disease categories: a classical inherited bone marrow failure syndrome and a 'ribosomopathy'. The description of DBA as a ribosomopathy has provided a context for scientific inquiry analogous to the description of Fanconi anemia as a disorder of DNA repair.
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