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Perspectives of current understanding and therapeutics of Diamond-Blackan anemia

Liu, Yang LU and Karlsson, Stefan LU (2023) In Leukemia
Abstract

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure disorder characterized by erythroid hypoplasia. It primarily affects infants and is often caused by heterozygous allelic variations in ribosomal protein (RP) genes. Recent studies also indicated that non-RP genes like GATA1, TSR2, are associated with DBA. P53 activation, translational dysfunction, inflammation, imbalanced globin/heme synthesis, and autophagy dysregulation were shown to contribute to disrupted erythropoiesis and impaired red blood cell production. The main therapeutic option for DBA patients is corticosteroids. However, half of these patients become non-responsive to corticosteroid therapy over prolonged treatment and have to be given blood... (More)

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure disorder characterized by erythroid hypoplasia. It primarily affects infants and is often caused by heterozygous allelic variations in ribosomal protein (RP) genes. Recent studies also indicated that non-RP genes like GATA1, TSR2, are associated with DBA. P53 activation, translational dysfunction, inflammation, imbalanced globin/heme synthesis, and autophagy dysregulation were shown to contribute to disrupted erythropoiesis and impaired red blood cell production. The main therapeutic option for DBA patients is corticosteroids. However, half of these patients become non-responsive to corticosteroid therapy over prolonged treatment and have to be given blood transfusions. Hematopoietic stem cell transplantation is currently the sole curative option, however, the treatment is limited by the availability of suitable donors and the potential for serious immunological complications. Recent advances in gene therapy using lentiviral vectors have shown promise in treating RPS19-deficient DBA by promoting normal hematopoiesis. With deepening insights into the molecular framework of DBA, emerging therapies like gene therapy hold promise for providing curative solutions and advancing comprehension of the underlying disease mechanisms.

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Contribution to journal
publication status
in press
subject
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Leukemia
publisher
Nature Publishing Group
external identifiers
  • pmid:37973818
  • scopus:85176723084
ISSN
0887-6924
DOI
10.1038/s41375-023-02082-w
language
English
LU publication?
yes
id
f3eb102f-71ea-4b41-a556-be9dee2615b8
date added to LUP
2024-01-10 14:01:52
date last changed
2024-04-25 10:00:39
@article{f3eb102f-71ea-4b41-a556-be9dee2615b8,
  abstract     = {{<p>Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure disorder characterized by erythroid hypoplasia. It primarily affects infants and is often caused by heterozygous allelic variations in ribosomal protein (RP) genes. Recent studies also indicated that non-RP genes like GATA1, TSR2, are associated with DBA. P53 activation, translational dysfunction, inflammation, imbalanced globin/heme synthesis, and autophagy dysregulation were shown to contribute to disrupted erythropoiesis and impaired red blood cell production. The main therapeutic option for DBA patients is corticosteroids. However, half of these patients become non-responsive to corticosteroid therapy over prolonged treatment and have to be given blood transfusions. Hematopoietic stem cell transplantation is currently the sole curative option, however, the treatment is limited by the availability of suitable donors and the potential for serious immunological complications. Recent advances in gene therapy using lentiviral vectors have shown promise in treating RPS19-deficient DBA by promoting normal hematopoiesis. With deepening insights into the molecular framework of DBA, emerging therapies like gene therapy hold promise for providing curative solutions and advancing comprehension of the underlying disease mechanisms.</p>}},
  author       = {{Liu, Yang and Karlsson, Stefan}},
  issn         = {{0887-6924}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{Perspectives of current understanding and therapeutics of Diamond-Blackan anemia}},
  url          = {{http://dx.doi.org/10.1038/s41375-023-02082-w}},
  doi          = {{10.1038/s41375-023-02082-w}},
  year         = {{2023}},
}