Danazol: An Effective and Underutilised Treatment Option in Diamond-Blackfan Anaemia

Chai, Kern Y.; Quijano, Cara J.; Chiruka, Shingirai

doi:10.1155/2019/4684156

Cited by 6 publications

(7 citation statements)

References 35 publications

(47 reference statements)

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“…Danazol, a synthetic androgen compound that inhibits pituitary gonadotrophins, had a positive effect on hemoglobin levels in DBA patients [ 55 ]. This follow-up is based on the observation that males have higher hemoglobin levels than females [ 56 ], although the mechanisms of action of Danazol remain unclear.…”

Section: Ribosomopathies With Specific Correctionsmentioning

confidence: 99%

Ribosomopathies: New Therapeutic Perspectives

Orgebin

Lamoureux

Isidor

et al. 2020

Cells

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Ribosomopathies are a group of rare diseases in which genetic mutations cause defects in either ribosome biogenesis or function, given specific phenotypes. Ribosomal proteins, and multiple other factors that are necessary for ribosome biogenesis (rRNA processing, assembly of subunits, export to cytoplasm), can be affected in ribosomopathies. Despite the need for ribosomes in all cell types, these diseases result mainly in tissue-specific impairments. Depending on the type of ribosomopathy and its pathogenicity, there are many potential therapeutic targets. The present manuscript will review our knowledge of ribosomopathies, discuss current treatments, and introduce the new therapeutic perspectives based on recent research. Diamond–Blackfan anemia, currently treated with blood transfusion prior to steroids, could be managed with a range of new compounds, acting mainly on anemia, such as L-leucine. Treacher Collins syndrome could be managed by various treatments, but it has recently been shown that proteasomal inhibition by MG132 or Bortezomib may improve cranial skeleton malformations. Developmental defects resulting from ribosomopathies could be also treated pharmacologically after birth. It might thus be possible to treat certain ribosomopathies without using multiple treatments such as surgery and transplants. Ribosomopathies remain an open field in the search for new therapeutic approaches based on our recent understanding of the role of ribosomes and progress in gene therapy for curing genetic disorders.

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Section: Ribosomopathies With Specific Correctionsmentioning

confidence: 99%

Ribosomopathies: New Therapeutic Perspectives

Orgebin

Lamoureux

Isidor

et al. 2020

Cells

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“…Danazol is another agent that can be used as immunosuppressive drug. It has properties of inhibiting TNF-alpha and IL-1 (Chai et al, 2019). It had shown its effectiveness in humans treating aplastic anemia, myelodysplasia, myelofibrosis, pure red cell aplasia, and bone marrow failure syndrome (Chai et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…It has properties of inhibiting TNF-alpha and IL-1 (Chai et al, 2019). It had shown its effectiveness in humans treating aplastic anemia, myelodysplasia, myelofibrosis, pure red cell aplasia, and bone marrow failure syndrome (Chai et al, 2019). Danazol has effects of decreasing macrophage Fc receptor expression, reducing the binding of antibodies to RBCs, stabilizing the RBC membranes, and alteration of T-cell regulation (Whitley and Day, 2011).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Danazol as an adjunctive therapy in dogs with immune-mediated hemolytic anemia

Park²,

Song

2022

Korean J. Vet. Serv

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Immune-mediated hemolytic anemia (IMHA) is autoimmune disease which is anemia caused by own immune system destroying the red blood cells (RBC). It can be diagnosed with spherocytosis, positive auto-agglutination of RBCs and direct antiglobulin test (DAT, Coomb's test). The treatment for IMHA are blood transfusion, immunosuppressive agents including glucocorticoids and other supportive therapies. Danazol is synthetic androgen that has effect of interfering the autoimmune reaction to RBCs. It can be used as an adjunctive agent in addition to glucocorticoids. To investigate its effectiveness, the medical records of 10 IMHA-diagnosed dogs were evaluated. All subjects were treated with blood transfusion, prednisolone, mycophenolate mofetil, and intravenous human immunoglobulin G. Additionally, 6 subjects were administered with danazol and 4 subjects were not. The results of initial blood examination and responses to the treatment for IMHA were compared between the groups. There were significant differences in the number of blood transfusions; once in group with danazol, twice in group without danazol, duration of recovery to normal hematocrit; 7.67±3.08 days in group with danazol, 22.00±5.66 days in group without danazol, and hospitalization; 5.17±0.75 days in group with danazol, 12.75±2.22 days in group without danazol. Therefore, danazol has potential effective on treating IMHA for rapid improvement.

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“…6 In ineffective erythropoiesis, there is an imbalance due to an increased proliferation of erythroid progenitors accompanied by increased apoptosis and decreased erythrocyte 71,72 Ineffective erythropoiesis leads to a of anemia-related blood diseases, including myelodysplastic syndrome (MDS), β-thalassemia (β-TM), and Diamond-Blackfan anemia (DBA). [72][73][74] Ineffective erythropoiesis, erythroid hyperplasia, and anemia phenotypes have been reported in the miR-142-/-mouse model. MiR-451/144 deficiency leads to erythroid hyperplasia and mild anemia, whereas miRNAs (eg, miR-150, miR-223, miR-15a, and miR-24) are upregulated in individuals with persistent injury, thereby inhibiting erythropoiesis and resulting in the development of persistent injury-related anemia.…”

Section: Diseases Related To Gene Post-transcriptional Dysregulation ...mentioning

confidence: 99%

Post-transcriptional regulation of erythropoiesis

Zhang

et al. 2023

Blood Science

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Erythropoiesis is a complex, precise, and lifelong process that is essential for maintaining normal body functions. Its strict regulation is necessary to prevent a variety of blood diseases. Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels, signal transduction, and various epigenetic modifications. In recent years, research on post-transcriptional levels in erythropoiesis has expanded significantly. The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis. RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell, yielding mRNA with dynamic translation efficiency. Noncoding RNAs, such as microRNAs and lncRNAs, are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis. N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination. This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases, and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis. These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.

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Danazol: An Effective and Underutilised Treatment Option in Diamond-Blackfan Anaemia

Cited by 6 publications

References 35 publications

Ribosomopathies: New Therapeutic Perspectives

Ribosomopathies: New Therapeutic Perspectives

Effectiveness of Danazol as an adjunctive therapy in dogs with immune-mediated hemolytic anemia

Post-transcriptional regulation of erythropoiesis

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