Division of Rheumatology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Korean J Intern Med. 2020 Mar;35(2):457-464. doi: 10.3904/kjim.2018.247. Epub 2019 Oct 25.
BACKGROUND/AIMS: Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS.
Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed.
The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance.
Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.
背景/目的：骨髓增生异常综合征（MDS）是由造血前体细胞的遗传和表观遗传改变以及免疫失调引起的。大约 20%的 MDS 患者会发展为自身免疫性疾病（AID）。在这里，我们研究了 MDS 患者的特定基因突变是否与 AID 相关。
对 73 例 MDS 患者的 88 种与髓系恶性肿瘤相关的基因突变进行测序。然后分析这些突变与 AID 之间的关系。
73 例 MDS 患者的中位年龄为 70 岁（四分位距，56 至 75），其中 49 例（67.1%）为男性。73 例患者中有 16 例（21.9%）出现 AID。在 57 例（78.1%）患者中检测到突变。有或没有 AID 的 MDS 患者的突变百分比（68.8%比 80.7%，p = 0.32）和平均突变数（1.8 ± 1.6 比 2.2 ± 1.8，p = 0.34）相似。然而，有 AID 的患者中 TET2 突变率明显高于无 AID 的患者（分别为 31.3%和 5.3%；p = 0.001）。所有 TET2 突变均为具有强烈临床意义的变异。
MDS 患者 TET2 突变可能与发生 AID 的风险增加有关。
