Impact of TET2 deficiency on iron metabolism in erythroblasts

Inokura, Kyoko; Fujiwara, Tohru; Saito, Kei; Iino, Tatsuya; Hatta, Shunsuke; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Shimoda, Kazuya; Harigae, Hideo

doi:10.1016/j.exphem.2017.01.002

Cited by 11 publications

(8 citation statements)

References 54 publications

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“…Using functional assays, the authors also established that TET2 plays a cytoprotective function in iron homeostasis against oxidative stress during erythropoiesis. In contrast, Inokura and colleagues [16], using cell sorting of murine bone marrow erythroid populations, observed that Tet2 mRNA levels is reduced at latter erythroid differentiation stages. However, the researchers observed that Tet2 knockdown mice present mild normocytic anemia, and downregulation/methylation of heme biosynthesis and iron metabolism-related genes [16], corroborating the hypothesis that TET2 plays a key role during normal erythropoiesis.…”

Section: Discussionmentioning

confidence: 87%

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

et al. 2017

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Background: Tet methylcytosine dioxygenase 2 (TET2) is frequently mutated and/or downregulated in myeloid neoplasm, including myelodysplastic syndromes. Despite the extensive studies, the specific contribution of TET2 in disease phenotype of myeloid neoplasms is not fully elucidated. Recent findings have grown attention on the role of TET2 in normal and malignant erythropoiesis. Methods: In the present study, we investigated TET2 mRNA levels by quantitative PCR during erythropoietin-induced erythroid differentiation CD34 + cells from healthy donor and myelodysplastic syndrome patients. Statistical analyses were performed using the ANOVA and Bonferroni post hoc test and a p-value <0.05 was considered statically significant. Results: TET2 expression is upregulated during erythroid differentiation of CD34 + cells from healthy donor and myelodysplastic syndrome patients. Conclusions: Our findings corroborate that TET2 is involved in the erythrocyte differentiation.

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Section: Discussionmentioning

confidence: 87%

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

et al. 2017

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“… 28 , 29 Some patients with MDS show TET2 mutation, which has been correlated with the dysregulation of several genes involved in iron metabolism. 30 …”

Section: Iron Overload Mechanisms In Mds Patientsmentioning

confidence: 99%

Prognostic Factors and Clinical Considerations for Iron Chelation Therapy in Myelodysplastic Syndrome Patients

Parisi¹,

Finelli²

2021

JBM

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Iron chelation therapy (ICT) is an important tool in the treatment of transfusion-dependent lower-risk myelodysplastic syndrome (MDS) patients. ICT is effective in decreasing iron overload and consequently in limiting its detrimental effects on several organs, such as the heart, liver, and endocrine glands. Besides this effect, ICT also proved to be effective in improving peripheral cytopenia in a significant number of MDS patients, thus further increasing the clinical interest of this therapeutic tool. In the first part of the review, we will analyze the toxic effect of iron overload and its mechanism. Subsequently, we will revise the clinical role of ICT in various subsets of MDS patients (low, intermediate, and high risk MDS, patients who are candidates for allogeneic stem cell transplantation).

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“…-TET2 mutations: (only in a subset of patients with MDS) may be involved in iron metabolism and in heme biosynthesis in the erythroblasts. Studies using TET2 knockdown mouse models have shown high serum and mitochondrial ferritin levels and dysregulation in a number of genes involved in iron metabolism (23).…”

Section: Definition Of a Genetic Profile Predisposing For Iron Overloadmentioning

confidence: 99%

From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox

et al. 2021

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Iron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy.

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Impact of TET2 deficiency on iron metabolism in erythroblasts

Cited by 11 publications

References 54 publications

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

TET2 is upregulated during erythroid differentiation of CD34+ cells from healthy donors and myelodysplastic syndrome patients

Prognostic Factors and Clinical Considerations for Iron Chelation Therapy in Myelodysplastic Syndrome Patients

From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox

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