Short telomere length and its correlation with gene mutations in myelodysplastic syndrome.
Short telomere length and its correlation with gene mutations in myelodysplastic syndrome.
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DOI：
10.1186/s13045-016-0287-9
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发表时间：
2016-07-28
影响因子：
28.5
通讯作者：
Lee DS
中科院分区：
文献类型：
--
作者：
Hwang SM;Kim SY;Kim JA;Park HS;Park SN;Im K;Kim K;Kim SM;Lee DS
端粒磨损可导致基因组不稳定和癌症进展。有人提出，最短端粒而非平均端粒长度（TL）对细胞活力至关重要。一些研究表明骨髓增生异常综合征（MDS）患者的端粒长度较短，但关键的短端粒以及个体患者内端粒长度的变异性尚未得到评估。因此，我们旨在研究MDS患者的端粒长度，并评估端粒长度与MDS中反复出现的基因突变的关联。
我们通过定量荧光原位杂交（Q - FISH）技术在单细胞水平上测量了58例MDS患者诊断样本的骨髓有核细胞的端粒长度，并分析了患者体内端粒长度的最小值、中位数、平均值、标准差、第0到第10百分位端粒长度的平均值，以及端粒长度短于正常对照（NC）最低第10百分位的细胞比例。还评估了端粒长度与临床参数、细胞遗传学结果和基因突变的相关性。
与正常对照相比，MDS患者表现出端粒磨损且分布较窄（分别为P < 0.001，P = 0.018）。有突变的患者中端粒长度短（低于正常对照最低第10百分位）的细胞明显较少（P = 0.017），但除CSF3R突变外，根据突变/细胞遗传学异常未发现端粒长度存在差异。然而，那些端粒长度短的细胞比例高（≥80%）的患者总体生存期较差（P = 0.021），并且这是一个独立的预后因素，与TP53、U2AF1突变以及高骨髓原始细胞计数一样（分别为P = 0.044、0.001、0.004、0.012）。
决定细胞命运的最短端粒长度在MDS中明显更短，且端粒长度短的细胞负担更高，这与生存期差相关，提示需要通过Q - FISH在单细胞中测量端粒长度。
本文的网络版（doi:10.1186/s13045 - 016 - 0287 - 9）包含补充材料，授权用户可获取。
Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH. The online version of this article (doi:10.1186/s13045-016-0287-9) contains supplementary material, which is available to authorized users.