2. Academic Validation
  3. Loss of FTH1 Induces Ferritinophagy-Mediated Ferroptosis in Anaemia of Myelodysplastic Syndromes

Loss of FTH1 Induces Ferritinophagy-Mediated Ferroptosis in Anaemia of Myelodysplastic Syndromes

  • J Cell Mol Med. 2025 Jan;29(1):e70350. doi: 10.1111/jcmm.70350.
Liyan Yang 1 2,  Mengying Zhang 1 2,  Mengyuan Liu 1 2,  Yating Yu 1 2,  Yue Zhang 1 2,  Jinyue Yang 1 2,  Limin Xing 1 2,  Zonghong Shao 1 2,  Huaquan Wang 1 2
Affiliations

Affiliations

  • 1 Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, China.
  • 2 Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, China.
PMID: 39804099 DOI: 10.1111/jcmm.70350
Abstract

Single-cell Sequencing of lineage negative (Lin-) cells from patients with myelodysplastic syndromes (MDS) revealed a reduction in ferritin heavy chain 1 (FTH1) levels, yet the significance of this decrease in FTH1 in the pathophysiology of MDS remains unclear. In this study, we evaluated the role of FTH1 in patients with MDS. The mRNA expression of FTH1 in GlycoA+ nucleated erythrocytes from MDS patients was significantly lower than that in control group. FTH1 was implicated in both ferritinophagy and Ferroptosis in MDS patients, processes that are linked to the development of anaemia. To further validate our observations, we employed shRNA to knock down the FTH1 gene in K562 and SKM1 cells. This knockdown confirmed that the elevated Ferroptosis levels observed after FTH1 depletion were indeed due to the induction of ferritinophagy. Hemin stimulation promoted the differentiation of K562 cells, while downregulation of FTH1 gene expression had an impact on erythroid differentiation and haemoglobin synthesis. Taken together, our results suggest that FTH1-mediated ferritinophagy may represent a novel therapeutic target for MDS.

Keywords

FTH1; anaemia; ferritinophagy; ferroptosis; myelodysplastic syndromes.

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