In myelodysplastic syndromes with ring sideroblasts (MDS-RS), the iron deposited in the mitochondria of RS is present in the form of mitochondrial ferritin (FTMT), but it is unknown whether FTMT overexpression is the cause or the result of mitochondrial iron deposition. Lentivirus FTMT-transduced CD34(+) bone marrow cells from seven healthy donors and CD34(+) cells from 24 patients with MDS-RS were cultured according to a procedure that allowed the expansion of high numbers of erythroid progenitors. These cells were used to investigate the possible influence of experimentally-induced FTMT overexpression on normal erythropoiesis and the functional effects of FTMT in sideroblastic erythropoiesis. In MDS-RS progenitors, FTMT overexpression was associated with reduced cytosolic ferritin levels, increased surface transferrin receptor expression and reduced cell proliferation; FTMT effects were independent of SF3B1 mutation status. Similarly, FTMT overexpressing normal erythroid progenitors were characterized by reduced cytosolic ferritin content and increased CD71 expression, and also by higher apoptotic rate in comparison with the FTMT- controls. Significantly lower levels of STAT5 phosphorylation following erythropoietin stimulation were found in both sideroblastic and normal FTMT(+) erythroid cells compared to the FTMT- cells. In conclusion, experimental overexpression of FTMT may modify mitochondrial iron availability and lead to ineffective erythropoiesis.

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.12316DOI Listing

Publication Analysis

Top Keywords

erythroid progenitors
12
ftmt overexpression
12
mitochondrial ferritin
8
overexpression normal
8
ftmt
8
mitochondrial iron
8
reduced cytosolic
8
cytosolic ferritin
8
overexpression
5
cells
5

Similar Publications

The purpose of the study was to investigate the effects of exercise training on the bone marrow immune microenvironment and on minimal residual disease of multiple myeloma patients who completed first-line induction treatment. Eight multiple myeloma patients underwent 5 months of exercise training along with standard medical treatment. Eight age- and sex-matched patients who received medical treatment only, served as controls.

View Article and Find Full Text PDF

Skeletal Site-Specific Lipid Profile and Hematopoietic Progenitors of Bone Marrow Adipose Tissue in Patients Undergoing Primary Hip Arthroplasty.

Metabolites

January 2025

Group for Hematology and Stem Cells, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.

Background/objectives: Bone marrow adipose tissue (BMAT) has been described as an important biomechanic and lipotoxic factor with negative impacts on skeletal and hematopoietic system regeneration. BMAT undergoes metabolic and cellular adaptations with age and disease, being a source of potential biomarkers. However, there is no evidence on the lipid profile and cellularity at different skeletal locations in osteoarthritis patients undergoing primary hip arthroplasty.

View Article and Find Full Text PDF

Human Oncostatin M deficiency underlies an inherited severe bone marrow failure syndrome.

J Clin Invest

January 2025

Laboratory of Genome Dynamics in the Immune, INSERM UMR 116, Équipe Labellisée LIGUE 2023, Paris, France.

Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM.

View Article and Find Full Text PDF

Myelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!