文章：

严重无效红细胞生成影响骨髓增生异常综合征的预后：基于单中心776例患者的分析

Severe ineffective erythropoiesis discriminates prognosis in myelodysplastic syndromes: analysis based on 776 patients from a single centre

原文发布日期：2020-08-14

DOI: 10.1038/s41408-020-00349-4

类型: Article

开放获取: 是

英文摘要：

The underlying mechanisms and clinical significance of ineffective erythropoiesis in myelodysplastic syndromes (MDS) remain to be fully defined. We conducted the ex vivo erythroid differentiation of megakaryocytic-erythroid progenitors (MEPs) from MDS patients and discovered that patient-derived erythroblasts exhibit precocity and premature aging phenotypes, partially by inducing the pro-aging genes, like ERCC1. Absolute reticulocyte count (ARC) was chosen as a biomarker to evaluate the severity of ineffective erythropoiesis in 776 MDS patients. We found that patients with severe ineffective erythropoiesis displaying lower ARC (<20 × 109/L), were more likely to harbor complex karyotypes and high-risk somatic mutations (p < 0.05). Lower ARCs are associated with shorter overall survival (OS) in univariate analysis (p < 0.001) and remain significant in multivariable analysis. Regardless of patients of lower-risk who received immunosuppressive therapy or higher-risk who received decitabine treatment, patients with lower ARC had shorter OS (p < 0.001). Whereas no difference in OS was found between patients receiving allo-hematopoietic stem cell transplantations (Allo-HSCT) (p = 0.525). Our study revealed that ineffective erythropoiesis in MDS may be partially caused by premature aging and apoptosis during erythroid differentiation. MDS patients with severe ineffective erythropoiesis have significant shorter OS treated with immunosuppressive or hypo-methylating agents, but may benefit from Allo-HSCT.
 

摘要翻译： 

骨髓增生异常综合征（MDS）中无效红细胞生成的潜在机制与临床意义尚未完全明确。我们通过体外诱导MDS患者巨核细胞-红系祖细胞（MEPs）的红系分化，发现患者来源的红系前体细胞呈现早熟及过早衰老表型，其部分机制是通过诱导ERCC1等促衰老基因表达。在776例MDS患者中，我们选择绝对网织红细胞计数（ARC）作为评估无效红细胞生成严重程度的生物标志物。研究发现，伴有严重无效红细胞生成（ARC<20×10⁹/L）的患者更易携带复杂核型及高危体细胞突变（p<0.05）。单因素分析显示较低ARC与较短总生存期（OS）相关（p<0.001），多因素分析中该相关性仍保持显著。无论接受免疫抑制治疗的低危患者或接受地西他滨治疗的高危患者，较低ARC均提示较短OS（p<0.001），而在接受异基因造血干细胞移植（Allo-HSCT）的患者中OS无显著差异（p=0.525）。本研究揭示MDS的无效红细胞生成可能部分源于红系分化过程中的过早衰老与凋亡。伴有严重无效红细胞生成的MDS患者接受免疫抑制或去甲基化药物治疗时OS显著缩短，但可能从Allo-HSCT中获益。

原文链接：

Severe ineffective erythropoiesis discriminates prognosis in myelodysplastic syndromes: analysis based on 776 patients from a single centre