Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond–Blackfan anemia

Wilkes, Mark C.; Scanlon, Vanessa; Shibuya, Aya; Celika, Alma-Martina; Eskin, Ascia; Chen, Zugen; Narla, Anupama; Glader, Bert; Roncarolo, Maria Grazia; Nelson, Stanley F.; Sakamoto, Kathleen M.

doi:10.1016/j.exphem.2022.04.005

Cited by 5 publications

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“…[31][32][33] Nemo-like kinase (NLK), a serine-threonine protein kinase, was reported hyperactive in erythroid progenitors from RPS19 and RPL11 knockdown human hematopoietic stem and progenitor cells (HSPCs). 34 Recently, Wilkes et al 35 reported that upregulated microRNA (miRNA), miR-34 and miR-30, are associated with the downregulation of SATB1, a global chromatin organizer and transcriptional factor, in a preclinical model of DBA, suggesting that epigenetics may play an important role in DBA pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Animal models of Diamond-Blackfan anemia: updates and challenges

et al. 2022

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Diamond-Blackfan anemia (DBA) is a ribosomopathy that is characterized by macrocytic anemia, congenital malformations, and early onset during childhood. Genetic studies have demonstrated that most patients carry mutations in one of the 20 related genes, most of which encode ribosomal proteins (RP). Treatment of DBA includes corticosteroid therapy, chronic red blood cell transfusion, and other forms of immunosuppression. Currently, hematopoietic stem cell transplantation is the only cure for DBA. Interestingly, spontaneous remissions occur in 10-20% of transfusion-dependent DBA patients. However, there is no consistent association between specific mutations and clinical manifestations. In the past decades, researchers have made significant progress in understanding the pathogenesis of DBA, but it remains unclear how the ubiquitous RP haploinsufficiency causes the erythroid-specific defect in hematopoiesis in DBA patients, and why there is a difference in penetrance and spontaneous remission among individuals who carry identical mutations. In this paper, we provide a comprehensive review of the development of DBA animal models and discuss the future research directions for these important experimental systems.

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