骨髓增生异常综合征患者有核红细胞自噬水平的研究

OBJECTIVE: To investigate the change of autophagy level of bone marrow nucleated red blood cell (RBC) in patients with myelodysplastic syndromes (MDS). METHODS: Fifty-four MDS patients and thirty-three controls were enrolled in this study. The mitophagy were observed by transmission electron microscopy (TEM). The level of autophagy-associated protein LC3B in GlycoA(+) nucleated RBC was measured by flow cytometry. The expressions of ULK1 and mTOR mRNA in GlycoA(+) nucleated RBC were measured by real-time PCR. The expression of the mitochondrial outer membrane protein TOM20 in GlycoA(+) nucleated RBC was detected by Western blot. RESULTS: Autophagosomes or autolysosomes were scarcely observed by TEM in MDS patients. The expression of LC3B in GlycoA(+) nucleated RBC in high-risk MDS patients (0.22±0.12) was significantly lower than that in normal controls (0.43±0.22, P<0.001), and lower than that in low-risk MDS patients (0.40±0.16, P=0.001). The expression of AMPK [0.26 (0.60)] in GlycoA(+) nucleated RBC in high-risk MDS patients was significantly lower than that in controls [1.00 (2.07), P<0.017). The expression of ULK1 mRNA in GlycoA(+) nucleated RBC in high-risk MDS patients [0.27 (3.31)] was significantly lower than that in controls [1.07 (4.41), P<0.017]. The level of mTOR mRNA in GlycoA(+) nucleated RBC in high-risk MDS patients [1.82 (3.74)] was significantly higher than that in controls [1.26 (1.38), P<0.017]. The level of LC3B in GlycoA(+) nucleated RBC was negatively correlated with the HGB (r=0.529, P=0.009) in high-risk MDS patients. The expression of mitochondrial outer membrane protein TOM20 in high-risk MDS patients was 9.42±4.42. CONCLUSION: Autophagy is impaired in nucleated RBC of MDS patients.