Impaired Mitophagy of Nucleated Erythroid Cells Leads to Anemia in Patients with Myelodysplastic Syndromes.

Huijuan Jiang,Chunyan Liu,Huaquan Wang,Zonghong Shao,Lifang Guo,Gaochao Zhang,Limin Xing,Ningbo Cui,Liyan Yang

doi:10.1155/2018/6328051

Huijuan Jiang, Chunyan Liu + Show 7 more

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https://doi.org/10.1155/2018/6328051

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Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by cytopenia and dysplasia. Anemia is the most common symptom in patients with MDS. Mitophagy and mitochondrial dysfunction might be involved in the development of MDS. In this study, we investigated the change of mitophagy in erythroid precursors in MDS patients. We found that NIX-mediated mitophagy was impaired in bone marrow nucleated red blood cells (NRBC) of MDS patients, associated with an increased amount of damaged mitochondria and increased ROS level which might lead to apoptosis and ineffective erythropoiesis. The results showed that the amount of mitochondria in GlycoA+ NRBC positively correlated with the count of ring sideroblasts in bone marrow samples. Meanwhile, the level of autophagy-associated marker LC3B in GlycoA+ NRBC had a positive correlation with hemoglobin (Hb) levels, and the amount of mitochondria in GlycoA+ NRBC had a negative correlation with Hb levels in high-risk MDS patients. Our results indicated that mitophagy might involve the pathogenesis of anemia associated with MDS. Autophagy might be a novel target in treatments of MDS patients.

Highlights

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective and dysplastic hematopoiesis [1]
MDS are a group of clonal hematopoietic stem cell disorders characterized by cytopenia, dysplasia, and a high risk of transformation to acute myeloid leukemia (AML)
The recent studies have reported that the loss of autophagy in murine hematopoietic stem/progenitor cells leads to bone marrow failure and development of age-related mitochondrial diseases such as MDS/AML [7, 13]

Summary

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective and dysplastic hematopoiesis [1]. The most common symptom of MDS patients is anemia [2]. Some researchers have reported that mitochondrial DNA mutant mice could develop macrocytic anemia as a MDS-like phenotype [7]. Mitophagy, which occurs to defective mitochondria following damage or stress, is selective mitochondria degradation by autophagy. By eliminating and degrading depolarized mitochondria, mitophagy plays a critical role in maintaining healthy pools of mitochondria [9, 10]. There exists a functional relationship between mitophagy and differentiation of hematopoietic stem cells (HSC) [11]. Impaired mitophagy might contribute to the development of MDS

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