RARE DISEASE
Diamond-Blackfan anemia
Diamond-Blackfan anemia
Diamond-Blackfan anemia
Synonyms: Congenital PRCA, Congenital pure red cell aplasia, Diamond-Blackfan anemia syndrome
Synonyms: Congenital PRCA, Congenital pure red cell aplasia, Diamond-Blackfan anemia syndrome
Synonyms: Congenital PRCA, Congenital pure red cell aplasia, Diamond-Blackfan anemia syndrome
Drug discovery
5
drugs
With orphan designations
Overview
Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by defective erythropoiesis, congenital anomalies (craniofacial, thumb, cardiac), and increased cancer risk. Caused by mutations in ribosomal protein genes (RPS19, RPL5, etc.), it typically presents with macrocytic anemia in infancy. Autosomal dominant inheritance occurs in 45% of cases, while 55% arise from de novo mutations. Diagnosis requires exclusion of acquired causes and genetic testing [1][6][12].
Therapies
First-line: Corticosteroids (80% initial response; long-term adverse effects limit use) [3][8][17]
Transfusion-dependent: Chronic red cell transfusions with iron chelation (deferasirox/deferoxamine) [8][13][16]
Definitive cure: HLA-matched hematopoietic stem cell transplantation (HSCT; >90% survival in children) [6][13][17]
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare hematological diseases, rare inborn errors of metabolism, rare neoplastic diseases, rare neurological diseases, rare otorhinolaryngological diseases, rare surgical maxillo-facial diseases, rare transplant-related disorders
Research Papers
394 drug discovery papers about Diamond-Blackfan anemia, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
394 drug discovery papers about Diamond-Blackfan anemia, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-23 | Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies
The translation of the transcriptome into a functional proteome is not a passive readout of mRNA abundance but a primary regulatory layer that actively shapes the oncogenic landscape. In hematologic malignancies, convergent oncogenic signaling pathways, including MYC, PI3K/AKT/mTOR, and tyrosine kinase fusions, directly reprogram the translational apparatus, driving a qualitative shift toward the selective synthesis of pro-survival, proliferative, and stemness-associated proteins. This deregulated program is orchestrated through multiple interconnected axes: the accelerated biogenesis of ribosomes within the nucleolus, the assembly of the eIF4F initiation complex, the activation of stress-adaptive programs like the integrated stress response (ISR), and a sophisticated layer of epitranscriptomic, tRNA, and RNA-binding protein-mediated regulation. Hematologic cancers provide a uniquely informative framework for deconstructing these processes, illustrated by inherited ribosomopathies, such as Diamond-Blackfan anemia syndrome and Shwachman-Diamond syndrome, which resolve the paradox of how ribosomal insufficiency can evolutionarily transition into malignant transformation. Beyond pathogenesis, the translational machinery represents a rich landscape of actionable vulnerabilities. Pharmacological targeting of RNA Polymerase I, eIF4A, and the ISR has demonstrated selective antitumor activity and synergistic potential with established therapies, including BCL-2 inhibition. This review synthesizes mechanistic and clinical evidence to position the ribosome as an active regulatory node rather than a passive decoding machine. We further examine the challenges facing the field, including translational plasticity under therapeutic pressure, the lack of validated companion biomarkers, and the emerging role of translational control in modulating anti-tumor immunity. Ultimately, we argue that defining the disease-specific translational states of leukemia and lymphoma is essential for the next generation of precision oncology, moving beyond genomic landscapes toward a proteomic-centered understanding of malignancy.
2026-07-15 | Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
Gene therapy is revolutionizing treatment paradigms for inherited haematological and immunological conditions. Recent successes, including the United States Food and Drug Administration (FDA) approval of gene therapy products for sickle cell disease and beta-thalassaemia, highlight the translational path of gene therapies for erythroid-specific disorders. In contrast, gene therapy development for other inherited erythroid disorders remains largely preclinical. Here, we examine the emerging landscape of gene therapies for inherited non-haemoglobinopathy erythroid disorders, focusing on the status of gene therapies for Diamond-Blackfan anaemia (DBA), pyruvate kinase deficiency (PKD), X-linked sideroblastic anaemia (XLSA), congenital erythropoietic porphyria (CEP) and congenital dyserythropoietic anaemia (CDA). We discuss the latest cellular engineering approaches being applied to developing therapies for these erythroid disorders and evolving strategies for conditioning and engraftment of modified cells. Despite the rarity of these disorders individually, several convergent biological and translational themes have emerged. Leveraging shared insights across diseases may accelerate clinical translation and broaden the curative potential of gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
2026-07-09 | [Inherited bone marrow failure syndromes].
Diamond-Blackfan anemia (DBA) is a classic example of an inherited bone marrow failure syndrome in the category of erythrocyte diseases. DBA mainly occurs due to ribosome dysfunction. In the peripheral blood, reticulocytes are reduced, and in the bone marrow, only erythroid cells are markedly reduced. DBA primarily develops in infants and is often caused by heterozygous allele mutations in ribosomal protein genes. Activation of p53, translation dysfunction, inflammatory signals, and imbalance of hemoglobin/heme synthesis have been shown to contribute to impaired erythropoiesis and decreased red blood cell production. Patients with DBA are primarily treated with steroids; however, half of these patients eventually become unresponsive to long-term steroid treatment and become transfusion-dependent. Hematopoietic cell transplantation is currently the only curative treatment. Recent advances in gene therapy using lentiviral vectors have shown potential in promoting normal hematopoiesis in the treatment of RPS19-deficient DBA.
2026-07-01 | Case study report on diamond-blackfan anemia
Diamond-Blackfan anemia is a rare inherited bone marrow disorder that usually occurs during infancy. It causes reduced production of red blood cells, leading to severe anemia, poor feeding, pallor, lethargy, and poor growth.
2026-06-30 | Factors determining successful allogeneic hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes
Introduction. Inherited bone marrow failure syndromes (IBMFS) constitute a heterogeneous group of rare genetic disorders associated with impaired hematopoiesis, congenital anomalies, and a high risk of transformation to myelodysplastic syndrome and acute myeloid leukemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for IBMFS. Aim: to identify factors determining the efficacy of allo-HSCT in pediatric patients with IBMFS. Materials and methods. This study analyzed data from 61 patients with IBMFS who had undergone allo-HSCT between 2005 and 2025 at the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation. Results. The median follow-up was 24 months. The overall survival (OS) at 1, 3, and 5 years post-transplantation was 88%, 85%, and 81%, respectively. The lowest 5-year OS was observed in the Fanconi anemia (47%) and Diamond–Blackfan anemia (86%) groups, whereas in the patients with other IBMFS the 5-year OS reached 100% (p = 0.003). Factors associated with improved survival included age younger than 5 years at transplantation (100% vs. 68%; p = 0.009), the use of myeloablative conditioning regimens (100% vs. 64.5%; p = 0.002), the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis (100% vs. 67%; p = 0.02), and successful engraftment (88% vs. 33%; p = 0.002). GVHD prophylaxis regimens without calcineurin inhibitors were associated with a lower incidence of grade II–IV acute GVHD (11% vs. 44%; p = 0.03) and a reduced need for switching immunosuppression (5% vs. 35%; p = 0.02). Donor type and degree of HLA matching did not significantly affect survival. Conclusion. Allo-HSCT is a highly effective treatment for children with IBMFS, providing a 5-year OS of 81%. The best outcomes are achieved with allo-HSCT performed at an early age (under 5 years), the use of myeloablative conditioning regimens (when not contraindicated), and with the addition of PTCy to GVHD prophylaxis. The lowest survival was observed in the patients with Fanconi anemia, highlighting the need for further refinement of treatment protocols for this patient group. PTCy-based GVHD prophylaxis regimens without calcineurin inhibitors reduce the incidence of acute GVHD and improve the tolerability of immunosuppression.
2026-07-23 | Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies
The translation of the transcriptome into a functional proteome is not a passive readout of mRNA abundance but a primary regulatory layer that actively shapes the oncogenic landscape. In hematologic malignancies, convergent oncogenic signaling pathways, including MYC, PI3K/AKT/mTOR, and tyrosine kinase fusions, directly reprogram the translational apparatus, driving a qualitative shift toward the selective synthesis of pro-survival, proliferative, and stemness-associated proteins. This deregulated program is orchestrated through multiple interconnected axes: the accelerated biogenesis of ribosomes within the nucleolus, the assembly of the eIF4F initiation complex, the activation of stress-adaptive programs like the integrated stress response (ISR), and a sophisticated layer of epitranscriptomic, tRNA, and RNA-binding protein-mediated regulation. Hematologic cancers provide a uniquely informative framework for deconstructing these processes, illustrated by inherited ribosomopathies, such as Diamond-Blackfan anemia syndrome and Shwachman-Diamond syndrome, which resolve the paradox of how ribosomal insufficiency can evolutionarily transition into malignant transformation. Beyond pathogenesis, the translational machinery represents a rich landscape of actionable vulnerabilities. Pharmacological targeting of RNA Polymerase I, eIF4A, and the ISR has demonstrated selective antitumor activity and synergistic potential with established therapies, including BCL-2 inhibition. This review synthesizes mechanistic and clinical evidence to position the ribosome as an active regulatory node rather than a passive decoding machine. We further examine the challenges facing the field, including translational plasticity under therapeutic pressure, the lack of validated companion biomarkers, and the emerging role of translational control in modulating anti-tumor immunity. Ultimately, we argue that defining the disease-specific translational states of leukemia and lymphoma is essential for the next generation of precision oncology, moving beyond genomic landscapes toward a proteomic-centered understanding of malignancy.
2026-07-15 | Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
Gene therapy is revolutionizing treatment paradigms for inherited haematological and immunological conditions. Recent successes, including the United States Food and Drug Administration (FDA) approval of gene therapy products for sickle cell disease and beta-thalassaemia, highlight the translational path of gene therapies for erythroid-specific disorders. In contrast, gene therapy development for other inherited erythroid disorders remains largely preclinical. Here, we examine the emerging landscape of gene therapies for inherited non-haemoglobinopathy erythroid disorders, focusing on the status of gene therapies for Diamond-Blackfan anaemia (DBA), pyruvate kinase deficiency (PKD), X-linked sideroblastic anaemia (XLSA), congenital erythropoietic porphyria (CEP) and congenital dyserythropoietic anaemia (CDA). We discuss the latest cellular engineering approaches being applied to developing therapies for these erythroid disorders and evolving strategies for conditioning and engraftment of modified cells. Despite the rarity of these disorders individually, several convergent biological and translational themes have emerged. Leveraging shared insights across diseases may accelerate clinical translation and broaden the curative potential of gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
2026-07-09 | [Inherited bone marrow failure syndromes].
Diamond-Blackfan anemia (DBA) is a classic example of an inherited bone marrow failure syndrome in the category of erythrocyte diseases. DBA mainly occurs due to ribosome dysfunction. In the peripheral blood, reticulocytes are reduced, and in the bone marrow, only erythroid cells are markedly reduced. DBA primarily develops in infants and is often caused by heterozygous allele mutations in ribosomal protein genes. Activation of p53, translation dysfunction, inflammatory signals, and imbalance of hemoglobin/heme synthesis have been shown to contribute to impaired erythropoiesis and decreased red blood cell production. Patients with DBA are primarily treated with steroids; however, half of these patients eventually become unresponsive to long-term steroid treatment and become transfusion-dependent. Hematopoietic cell transplantation is currently the only curative treatment. Recent advances in gene therapy using lentiviral vectors have shown potential in promoting normal hematopoiesis in the treatment of RPS19-deficient DBA.
2026-07-01 | Case study report on diamond-blackfan anemia
Diamond-Blackfan anemia is a rare inherited bone marrow disorder that usually occurs during infancy. It causes reduced production of red blood cells, leading to severe anemia, poor feeding, pallor, lethargy, and poor growth.
2026-06-30 | Factors determining successful allogeneic hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes
Introduction. Inherited bone marrow failure syndromes (IBMFS) constitute a heterogeneous group of rare genetic disorders associated with impaired hematopoiesis, congenital anomalies, and a high risk of transformation to myelodysplastic syndrome and acute myeloid leukemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for IBMFS. Aim: to identify factors determining the efficacy of allo-HSCT in pediatric patients with IBMFS. Materials and methods. This study analyzed data from 61 patients with IBMFS who had undergone allo-HSCT between 2005 and 2025 at the R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation. Results. The median follow-up was 24 months. The overall survival (OS) at 1, 3, and 5 years post-transplantation was 88%, 85%, and 81%, respectively. The lowest 5-year OS was observed in the Fanconi anemia (47%) and Diamond–Blackfan anemia (86%) groups, whereas in the patients with other IBMFS the 5-year OS reached 100% (p = 0.003). Factors associated with improved survival included age younger than 5 years at transplantation (100% vs. 68%; p = 0.009), the use of myeloablative conditioning regimens (100% vs. 64.5%; p = 0.002), the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis (100% vs. 67%; p = 0.02), and successful engraftment (88% vs. 33%; p = 0.002). GVHD prophylaxis regimens without calcineurin inhibitors were associated with a lower incidence of grade II–IV acute GVHD (11% vs. 44%; p = 0.03) and a reduced need for switching immunosuppression (5% vs. 35%; p = 0.02). Donor type and degree of HLA matching did not significantly affect survival. Conclusion. Allo-HSCT is a highly effective treatment for children with IBMFS, providing a 5-year OS of 81%. The best outcomes are achieved with allo-HSCT performed at an early age (under 5 years), the use of myeloablative conditioning regimens (when not contraindicated), and with the addition of PTCy to GVHD prophylaxis. The lowest survival was observed in the patients with Fanconi anemia, highlighting the need for further refinement of treatment protocols for this patient group. PTCy-based GVHD prophylaxis regimens without calcineurin inhibitors reduce the incidence of acute GVHD and improve the tolerability of immunosuppression.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
5 orphan drug designations for Diamond-Blackfan anemia.
5 orphan drug designations for Diamond-Blackfan anemia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Dasatinib | small molecules | EMA | 2026-06-19 | — | Consorcio Centro De Investigacion Biomedica En Red |
Autologous CD34+ enriched cells transduced with a self-inactivating lentiviral vector containing the codon-optimized RPS19 gene | gene therapies | EMA | 2021-11-12 | — | Consorcio Centro de Investigación Biomédica en Red |
Autologous CD34+ cells transfected with a lentiviral vector containing codon optimised RPS19 gene | gene therapies | EMA | 2021-08-20 | — | Medicinal Product Lifecycle Management |
CD34+ cells that have been transduced in vitro with a lentiviral vector carrying a codon-optimized sequence for expressing the wild type RPS19 protein | gene therapies | FDA | 2020-10-21 | — | Apriligen, Inc. |
Interleukin-3 human (recombinant) | proteins | FDA | 1991-05-20 | — | Immunex Corporation |
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