Effect of Glucocorticosteroids in Diamond-Blackfan Anaemia: Maybe Not as Elusive as It Seems.

Zuzana Macečková,Juan De Sanctis,Marian Hajdúch,Agáta Kubíčková

doi:10.3390/ijms23031886

Abstract

Diamond-Blackfan anaemia (DBA) is a red blood cell aplasia that in the majority of cases is associated with ribosomal protein (RP) aberrations. However, the mechanism by which this disorder leads to such a specific phenotype remains unclear. Even more elusive is the reason why non-specific agents such as glucocorticosteroids (GCs), also known as glucocorticoids, are an effective therapy for DBA. In this review, we (1) explore why GCs are successful in DBA treatment, (2) discuss the effect of GCs on erythropoiesis, and (3) summarise the GC impact on crucial pathways deregulated in DBA. Furthermore, we show that GCs do not regulate DBA erythropoiesis via a single mechanism but more likely via several interdependent pathways.

Highlights

Diamond-Blackfan Anaemia: MaybeHuman erythrocytes differ from other cells because of their particular shape, lack of organelles, and transportation of oxygen via haemoglobin
Even though GC-induced mTOR inactivation may lead to decreased proliferation of burst forming unit-erythroid (BFU-E) and colonyforming unit-erythroid (CFU-E) cells [82], stress-induced erythropoiesis may compensate for this [39] (Figure 3)
We suggest that GCs improve the Diamond-Blackfan anaemia (DBA) pathology via at least four relatively independent ways: (i) induction of BFU-E cell proliferation via stress erythropoiesis, (ii)regulation of P53 signalling, (iii) deactivation of c-Myc, and (iv) inhibition of mTOR signalling

Summary

Introduction

Human erythrocytes differ from other cells because of their particular shape, lack of organelles, and transportation of oxygen via haemoglobin. The efficient present review aims to analyse the possible that the development of more and targeted therapies withoutpathways glucocorticoid may be affected by GCs and improve pathology. The genetic variability of GCR can affect body mass index, bone density or coronary artery diseases, probability of developing type II diabetes and GC treatment outcome [33,34]. It has been shown that particular SNPs (rs6196 and rs860457) in GCR result in early onset of DBA, which can be caused by a modified GC response during embryogenesis [35]

The Primary Defect in DBA Cells

GCs and GATA1

Regulation of Ribosomal Stress and p53

Regulation of Enucleation through c-Myc

10. Conclusions