Erythropoiesis and Iron Homeostasis in Non-Transfusion-Dependent Thalassemia Patients with Extramedullary Hematopoiesis

Huang, Yumei; Liu, Rongrong; Wei, Xiaoyun; Liu, Jiaodi; Pan, Lingyuan; Yang, Gaohui; Lai, Yongrong

doi:10.1155/2019/4504302

Cited by 12 publications

(15 citation statements)

References 28 publications

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“…It needs to be further elucidated whether biological effects of ERFE and GDF15 in MDS are restricted to the regulation of iron metabolism and iron supply to proliferating erythroid progenitors. Although previous studies reported correlations between ERFE and GDF15 circulating levels with parameters of iron metabolism, 8,26,27 no strong correlations between ERFE and GDF15 expression in erythroid progenitors in MDS and available iron parameters were observed in our study. The correlation between ERFE expression and haemoglobin levels was very weak (Spearman r = −0·2322).…”

Section: Discussioncontrasting

confidence: 99%

High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes

et al. 2021

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Summary Ineffective erythropoiesis and iron overload are common in myelodysplastic syndromes (MDS). Erythroferrone (ERFE) and growth/differentiation factor 15 (GDF15) are two regulators of iron homeostasis produced by erythroid progenitors. Elevated systemic levels of ERFE and GDF15 in MDS are associated with dysregulated iron metabolism and iron overload, which is especially pronounced in MDS with SF3B1 gene mutations. However, the role of ERFE and GDF15 in MDS pathogenesis and their influence on disease progression are largely unknown. Here, we analyzed the expression of ERFE and GDF15 in CD71+ erythroid progenitors of n = 111 MDS patients and assessed their effects on patient survival. The expression of ERFE and GDF15 in MDS was highly aberrant. Unexpectedly, ERFE expression in erythroprogenitors was highly relevant for MDS prognosis and independent of International Prognostic Scoring System (IPSS) stratification. Although ERFE expression was increased in patients with SF3B1 mutations, it predicted overall survival (OS) in both the SF3B1wt and SF3B1mut subgroups. Of note, ERFE overexpression predicted superior OS in the IPSS low/Int‐1 subgroup and in patients with normal karyotype. Similar observations were made for GDF15, albeit not reaching statistical significance. In summary, our results revealed a strong association between ERFE expression and MDS outcome, suggesting a possible involvement of ERFE in molecular MDS pathogenesis.

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Section: Discussioncontrasting

confidence: 99%

High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes

et al. 2021

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“…In thalassemia, ineffective erythropoiesis induces the release of factors including growth differentiation factor 15 (GDF15), twisted gastrulation protein homolog 1 (TWSG1), Hypoxia Inducible Factor (HIF), and erythroferrone (ERFE), which can all inhibit hepcidin release. A negative correlation of GFD 15 with hepcidin corroborates the suppression of the iron regulatory protein and hepcidin [28] . Data of the present study illustrated the the presence of a significant negative correlation between serum ferritin and age of thalassemia onset, frequency of blood transfusions, as when hemolysis present early, this will need more frequent blood transfusions, which lead to significant elevation in serum ferritin level and ultimately iron overload.…”

Section: Discussionmentioning

confidence: 58%

Soluble Form of Transferrin Receptor as A Biomarker of Ineffective Erythropoiesis and Iron Overload in Pediatric Egyptian Patients with b-Thalassemia

Soliman¹,

Abd-Elhalim²,

El-Dahshan

2019

The Medical Journal of Cairo University

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Background: Beta-thalassemias (β -thalassemias) are a group of inherited blood disorders caused by reduced or absent synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. Thalassemia is the commonest hereditary hemolytic anemia in Egypt. Iron overload is a major complication of repeated blood transfusion in patients with thalassemia. Soluble Transferrin Receptor (sTfR), one of the main regulators of cellular iron homeostasis, is the truncated form of the tissue receptor. Aim of Study:This work was conducted to study the pathophysiology of iron overload in children with βthalassemia intermedia and thalassemia major and explore the possible utility of Soluble Transferrin Receptor (sTfR) for the evaluation of iron overload and ineffective erythropoiesis in pediatric Egyptian patients with ß thalassemia major, β -thalassemia intermedia and comparing this with the controls. Patients and Methods:This study was conducted on sixty β -thalassemia patients (30 β -thalassemia major and 30 βthalassemia intermedia) together with 30 age and sex matched controls. Patients were selected from the outpatient clinics of the Pediatric Hematology Unit and the Inpatients Hospital during the year 2017. Patients and control were subjected to clinical evaluation and complete blood count along with serum ferritin and sTfR levels by Enzyme-Linked Immunosorbent Assay (ELIZA) technique.Results: Both serum ferritin and sTfR levels were significantly higher in patients compared with controls and in patients with thalassemia major compared with those with thalassemia intermedia. Serum ferritin and sTfR levels were significantly positively correlated with patients' age and with each other. Each of them was negatively correlated with age of disease onset, frequency of blood transfusions and with hemoglobin level.Conclusion: Serum levels of ferritin and soluble transferrin receptor were significantly higher in both thalassemic groups in comparison to control group.

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“…Yumei Huang et al. reported a mean age of 27.5 years [ 25 ]. EMH is related to chronic and prolonged anaemia that leads to ineffective erythropoiesis.…”

Section: Discussionmentioning

confidence: 99%

Extramedullary haematopoiesis in patients with transfusion dependent β-thalassaemia (TDT): a systematic review

et al. 2022

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Introduction Around 5% of the world’s population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. Methods This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943. Results Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature ( N = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection. Conclusion EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM. KEY MESSAGES Extramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before. There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities. More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.

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Erythropoiesis and Iron Homeostasis in Non-Transfusion-Dependent Thalassemia Patients with Extramedullary Hematopoiesis

Cited by 12 publications

References 28 publications

High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes

High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes

Soluble Form of Transferrin Receptor as A Biomarker of Ineffective Erythropoiesis and Iron Overload in Pediatric Egyptian Patients with b-Thalassemia

Extramedullary haematopoiesis in patients with transfusion dependent β-thalassaemia (TDT): a systematic review

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Erythropoiesis and Iron Homeostasis in Non-Transfusion-Dependent Thalassemia Patients with Extramedullary Hematopoiesis

Cited by 12 publications

References 28 publications

High erythroferrone expression in CD71+ erythroid progenitors predicts superior survival in myelodysplastic syndromes

High erythroferrone expression in CD71+ erythroid progenitors predicts superior survival in myelodysplastic syndromes

Soluble Form of Transferrin Receptor as A Biomarker of Ineffective Erythropoiesis and Iron Overload in Pediatric Egyptian Patients with b-Thalassemia

Extramedullary haematopoiesis in patients with transfusion dependent β-thalassaemia (TDT): a systematic review

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High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes

High erythroferrone expression in CD71⁺ erythroid progenitors predicts superior survival in myelodysplastic syndromes