Congenital disorders of ribosome biogenesis and bone marrow failure

Abstract

Diamond Blackfan anemia (DBA) is a congenital bone marrow (BM) failure syndrome that typically results in macrocytic anemia within the first year of life. DBA is also associated with birth defects, increased incidence of cancer, and other cytopenias. Shwachman-Diamond syndrome (SDS) is a multisystem disease characterized by exocrine pancreatic dysfunction, impaired hematopoiesis, and leukemia predisposition. Other clinical features include skeletal, immunologic, hepatic, and cardiac disorders. Treatment for these BM failure syndromes, including stem cell transplantation (SCT), will be discussed in this review.

Figure 1.

DBA phenotype in zebrafish embryos injected with RPS19 morpholinos. (A,B) At 72 high-power field, there are fewer blood cells in zebrafish embryos injected with RPS19 morpholinos and there are only few cells in the heart region: 2.5 ng morpholino per embryo, O-dianizidine staining, 30 embryos per group. (C) Erythroid cells from the blood of a morphant embryo are variable in size; some look like erythroblasts. Zebrafish erythrocytes differ from mammalian cells in that both primitive and definitive cells are nucleated. Blood smears were prepared from individual embryos; the results are representative of 6 to 10 embryos. (D) The level of hemoglobin is lower in morphants at day 5 in dependence with morpholino dose [4]. This figure and research was originally published as Danilova N, Sakamoto KM, Lin S. Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood. 2008;112:5228-5237. © American Society of Hematology.