Diamond blackfan anemia: New paradigms for a "not so pure" inherited red cell aplasia.
Diamond Blackfan anemia (DBA) is a genetically and clinically heterogeneous disorder characterized by erythroid failure, congenital anomalies, and a predisposition to cancer. Faulty ribosome biogenesis is hypothesized to be the underlying defect, leading to erythroid failure due to accelerated apoptosis in affected erythroid progenitors/precursors. Since first observed in DBA, pro-apoptotic hematopoiesis has been recognized as a common mechanism for hematopoietic failure in virtually all of the inherited bone marrow failure syndromes. Inherited as an autosomal dominant trait, one of what appears to be multiple DBA genes, coding for ribosomal protein RPS19, has been cloned. The discovery of additional genes will no doubt clarify the molecular pathophysiology of this disorder. Even within families, individuals may vary dramatically as to the degree of anemia, treatment response, and the presence of congenital anomalies. The study of DBA has been facilitated by the creation of international patient registries that provide more reliable information regarding clinical presentation, genetics, and outcome, as well as descriptions of congenital malformations and cancer predisposition, than can be culled from the literature. Analysis of registry data has led to improvements in clinical care and provides patients and research specimens for clinical and laboratory investigations.
Lipton
Jeffrey M
JM
Division of Pediatric Hematology/Oncology and Stem Cell Transplantation, Schneider Children's Hospital, Albert Einstein College of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA. jlipton@lij.edu
D029503:Anemia, Diamond-Blackfan / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D012010:Red-Cell Aplasia, Pure / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome
D012269:Ribosomal Proteins; C040343:ribosomal protein S19