Diamond-Blackfan anemia

Blood. 2020 Sep 10;136(11):1262-1273. doi: 10.1182/blood.2019000947.


Diamond-Blackfan anemia (DBA) was the first ribosomopathy described and is a constitutional inherited bone marrow failure syndrome. Erythroblastopenia is the major characteristic of the disease, which is a model for ribosomal diseases, related to a heterozygous allelic variation in 1 of the 20 ribosomal protein genes of either the small or large ribosomal subunit. The salient feature of classical DBA is a defect in ribosomal RNA maturation that generates nucleolar stress, leading to stabilization of p53 and activation of its targets, resulting in cell-cycle arrest and apoptosis. Although activation of p53 may not explain all aspects of DBA erythroid tropism, involvement of GATA1/HSP70 and globin/heme imbalance, with an excess of the toxic free heme leading to reactive oxygen species production, account for defective erythropoiesis in DBA. Despite significant progress in defining the molecular basis of DBA and increased understanding of the mechanistic basis for DBA pathophysiology, progress in developing new therapeutic options has been limited. However, recent advances in gene therapy, better outcomes with stem cell transplantation, and discoveries of putative new drugs through systematic drug screening using large chemical libraries provide hope for improvement.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adenosine Deaminase / blood
  • Adenosine Deaminase / genetics
  • Anemia, Diamond-Blackfan* / diagnosis
  • Anemia, Diamond-Blackfan* / genetics
  • Anemia, Diamond-Blackfan* / metabolism
  • Anemia, Diamond-Blackfan* / therapy
  • Child, Preschool
  • Congenital Abnormalities / genetics
  • Diagnosis, Differential
  • Disease Management
  • Drug Resistance
  • Erythrocytes / enzymology
  • Fetal Growth Retardation / etiology
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / physiology
  • Genetic Heterogeneity
  • Genetic Therapy
  • Glucocorticoids / therapeutic use
  • HSP70 Heat-Shock Proteins / metabolism
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Infant, Newborn
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / genetics
  • Models, Biological
  • Mutation
  • Neoplastic Syndromes, Hereditary / genetics
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / physiology
  • Tumor Suppressor Protein p53 / physiology


  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Glucocorticoids
  • HSP70 Heat-Shock Proteins
  • Intercellular Signaling Peptides and Proteins
  • Ribosomal Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ADA2 protein, human
  • Adenosine Deaminase