Wang Na, Wang Fei, Shan Ningning, Sui Xiaohui, Xu Hongzhi
Department of Haematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
Acta Haematol. 2017;138(3):143-151. doi: 10.1159/000479546. Epub 2017 Sep 6.
Genomic sequencing technologies have identified isocitrate dehydrogenase (IDH) mutations in haematological malignancies. The prognostic implications of somatic IDH mutation (mIDH) in myelodysplastic syndromes (MDS) remain controversial.
Mutations in IDH1 and IDH2 were detected using genomic sequencing technologies in 97 patients with MDS.
Seven (7.2%) mutations were identified: 3 in IDH1 (all R132C) and 4 in IDH2 (3 R140Q and 1 R140L). The frequency of mutation was 16.6% (2/12) in refractory anaemia with excess blasts (RAEB)-1 and 14.7% (5/34) in RAEB-2. IDH1/2 mutations were closely associated with higher bone marrow blast counts (median 10.0 vs. 2.3%; p = 0.019) and lower absolute neutrophil counts (median 0.44 × 109/L vs. 1.21 × 109/L; p = 0.027). All IDH mutations were mutually exclusive and heterozygous. IDH mutations were not significantly correlated with any specific karyotype. Patients with IDH1 mutations exhibited shorter overall and progression-free survival (OS and PFS; p = 0.039 and p = 0.042, respectively), whereas IDH2 mutations did not affect OS or PFS (p = 0.560 and p = 0.218, respectively). Multivariate analysis indicated that IDH1 mutation (p = 0.018; hazard ratio [HR] 4.735; 95% confidence interval [CI] 1.299-17.264), karyotype risk (p = 0.036; HR 1.619; 95% CI 1.033-2.539) and the revised International Prognostic Scoring System risk category (p < 0.0001; HR 2.122; 95% CI 1.401-3.213) were independent inferior prognostic factors.
IDH1 mutation is associated with a poor prognosis.
基因组测序技术已在血液系统恶性肿瘤中鉴定出异柠檬酸脱氢酶（IDH）突变。骨髓增生异常综合征（MDS）中体细胞IDH突变（mIDH）的预后意义仍存在争议。
使用基因组测序技术检测了97例MDS患者的IDH1和IDH2突变。
共鉴定出7例（7.2%）突变：IDH1突变3例（均为R132C），IDH2突变4例（3例R140Q和1例R140L）。难治性贫血伴原始细胞增多（RAEB）-1型中的突变频率为16.6%（2/12），RAEB-2型中为14.7%（5/34）。IDH1/2突变与较高的骨髓原始细胞计数密切相关（中位数分别为10.0%对2.3%；p = 0.019），且与较低的绝对中性粒细胞计数相关（中位数分别为0.44×10⁹/L对1.21×10⁹/L；p = 0.027）。所有IDH突变均为互斥且杂合。IDH突变与任何特定核型均无显著相关性。IDH1突变患者的总生存期和无进展生存期较短（OS和PFS；分别为p = 0.039和p = 0.042），而IDH2突变不影响OS或PFS（分别为p = 0.560和p = 0.218）。多因素分析表明，IDH1突变（p = 0.018；风险比[HR] 4.735；95%置信区间[CI] 1.299 - 17.264）、核型风险（p = 0.036；HR 1.619；95% CI 1.033 - 2.539）和修订的国际预后评分系统风险类别（p < 0.0001；HR 2.122；95% CI 1.401 - 3.213）是独立的不良预后因素。
IDH1突变与不良预后相关。
