The soluble transferrin receptor in dysplastic erythropoiesis in myelodysplastic syndrome

Metzgeroth, Georgia; Rosée, Paul La; Kühn, Christian; Schultheis, Beate; Dorn-Beineke, Alexandra; Hehlmann, Rüdiger; Hastka, Jan

doi:10.1111/j.1600-0609.2007.00863.x

Cited by 8 publications

(9 citation statements)

References 26 publications

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“… 7 Interestingly, recently developed hepcidin agonists prevented low hepcidin-induced toxicity, preclinically, thus demonstrating the potential of these compounds to prevent iron loading erythropoietic activity in MDS, especially in RS-MDS. 25 , 40 Taken together, our data suggest a worsening over time of the ineffective erythropoiesis along with lower hepcidin levels in RS patients. 41 , 42 …”

Section: Discussionmentioning

confidence: 53%

“…In addition, sTFR levels decreased over time in TD patients, compatible with previously reported suppression of erythropoiesis by continued transfusions. 20 , 25 Interestingly, GDF15 increased over time in TD MDS patients and especially in those categorized as TD RS-MDS. Increased GDF15 has previously been associated with ineffective erythropoiesis, but not with TD-mediated suppression of erythropoiesis.…”

Section: Discussionmentioning

confidence: 97%

“… 26 , 27 Among others, sTFR levels are elevated in case of high erythroid proliferation rates, especially in combination with adequate iron supply, 27 as in diseases characterized by ineffective erythropoiesis, such as β-thalassemia syndromes, and levels are suppressed in case of decreased erythropoietic activity, as in anemia of chronic disease, and diseases with erythroid hypoplasia. 20 , 25 , 28 Earlier studies showed that sTFR levels are increased in MDS-RS, 5 including SF3B1-positive MDS patients. 11 …”

Section: Introductionmentioning

confidence: 98%

“… 5 , 9 , 22 However, its role in MDS is still a matter of debate due to conflicting results. 5 , 11 , 22 – 25 Twisted gastrulation factor 1 (TWSG1) and erythroferrone (ERFE) are also reported to have a suppressive function in hepatic hepcidin production, however, validated human assays are not available. 9 Of additional interest in iron homeostasis is sTFR.…”

Section: Introductionmentioning

confidence: 99%

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Labile plasma iron levels predict survival in patients with lower-risk myelodysplastic syndromes

et al. 2017

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Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Labile plasma iron levels predict survival in patients with lower-risk myelodysplastic syndromes

et al. 2017

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“…The sTfR level indicates erythropoietic activity and iron status of the organs [82]. sTfR is increased in thalassemia [67], congenital dyserythropoietic anemia [69, 81], and sideroblastic anemia [83]. All of these observations make sTfR a strong candidate for erythroid regulation of hepcidin and iron.…”

Section: Molecules Released From Erythroblastsmentioning

confidence: 99%

Iron Loading and Overloading due to Ineffective Erythropoiesis

Tanno

Miller

2010

Advances in Hematology

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Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.

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Disorders of Red Cell Production and the Iron-Loading Anemias

Rivella

2011

Iron Physiology and Pathophysiology in Humans

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The soluble transferrin receptor in dysplastic erythropoiesis in myelodysplastic syndrome

Cited by 8 publications

References 26 publications

Labile plasma iron levels predict survival in patients with lower-risk myelodysplastic syndromes

Labile plasma iron levels predict survival in patients with lower-risk myelodysplastic syndromes

Iron Loading and Overloading due to Ineffective Erythropoiesis

Disorders of Red Cell Production and the Iron-Loading Anemias

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