Severely impaired terminal erythroid differentiation as an independent prognostic marker in myelodysplastic syndromes
Severely impaired terminal erythroid differentiation as an independent prognostic marker in myelodysplastic syndromes
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严重受损的终末红系分化作为骨髓增生异常综合征的独立预后标志
DOI：
10.1182/bloodadvances.2018018440
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发表时间：
2018-06-26
期刊：
影响因子：
7.5
通讯作者：
Raza, Azra
中科院分区：
文献类型：
--
作者：
Ali, Abdullah Mahmood;Huang, Yumin;Raza, Azra
贫血是大多数骨髓增生异常综合征 (MDS) 患者的决定性特征，但红细胞生成缺陷尚未得到很好的表征。我们通过测量血型糖蛋白 A、条带 3 和整合素 α-4 的表面表达，检查了来自 221 个样本（MDS，n = 205，来自 113 名独特患者；正常，n = 16）的红系终末分化 (TED) 期间新鲜获得的骨髓 (BM) 样本的阶段特异性异常。寻找 TED 存在与否以及红细胞停滞特定阶段之间的临床和生物学关联。在 27% 的 MDS 样本 (56/205) 中，没有通过终末分化红细胞的整合素 α-4 和带 3 的表面表达记录可量化的 TED。缺乏可量化的 TED 与显着较差的总生存期（56 个月 vs 103 个月，P = .0001）和 SRSF2 突变（7/23，P < .05）相关。在多变量 Cox 比例风险回归分析中，TED 的缺失在国际预后评分系统修订版 (IPSS-R) 类别、骨髓/红细胞比率和多个基因突变中仍然具有独立显着性。在 149/205 个 MDS 样本中，经历 TED 的细胞比例在连续阶段中并未遵循预期的 1:2:4:8:16 倍增模式。 TED 的缺乏成为 MDS 所有 IPSS-R 类别中总体生存率较差的强大独立预后标志，并且 SRSF2 突变更频繁地与 TED 的缺乏相关。
Anemia is the defining feature in most patients with myelodysplastic syndromes (MDS), yet defects in erythropoiesis have not been well characterized. We examined freshly obtained bone marrow (BM) samples for stage-specific abnormalities during terminal erythroid differentiation (TED) from 221 samples (MDS, n = 205 from 113 unique patients; normal, n = 16) by measuring the surface expression of glycophorin A, band 3, and integrin alpha-4. Clinical and biologic associations were sought with presence or absence of TED and the specific stage of erythroid arrest. In 27% of MDS samples (56/205), there was no quantifiable TED documented by surface expression of integrin alpha-4 and band 3 by terminally differentiating erythroblasts. Absence of quantifiable TED was associated with a significantly worse overall survival (56 vs 103 months, P = .0001) and SRSF2 mutations (7/23, P < .05). In a multivariable Cox proportional hazards regression analysis, absence of TED remained independently significant across International Prognostic Scoring System-Revised (IPSS-R) categories, myeloid/erythroid ratio, and mutations in several genes. In 149/205 MDS samples, the proportion of cells undergoing TED did not follow the expected 1:2:4:8:16 doubling pattern in successive stages. Absence of TED emerged as a powerful independent prognostic marker of poor overall survival across all IPSS-R categories in MDS, and SRSF2 mutations were more frequently associated with absence of TED.