Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Leukemia. 2012 Jan;26(1):101-5. doi: 10.1038/leu.2011.298. Epub 2011 Oct 28.
Unlike the case with acute myeloid leukemia, there is limited information on the prognostic impact of isocitrate dehydrogenase (IDH) mutations in myelodysplastic syndromes (MDS). In the current study of 277 patients with MDS, IDH mutations were detected in 34 (12%) cases: 26 IDH2 (all R140Q) and 8 IDH1 (6 R132S and 2 R132C). Mutational frequency was 4% (2 of 56) in refractory anemia with ring sideroblasts, 12% (16 of 130) in refractory cytopenia with multilineage dysplasia, 14% (2 of 14) in MDS-unclassifiable, 14% (6 of 42) in refractory anemia with excess blasts (RAEB)-1 and 23% (8 of 35) in RAEB-2. Normal karyotype was noted in all but one IDH1-mutated cases and 13 IDH2-mutated cases. Multivariable analysis identified presence of mutant IDH1 (P=0.0004; hazard ration 4.0, 95% confidence interval 1.9-8.8), revised International Prognostic Scoring System risk category (P<0.0001), and red cell transfusion need (P=0.002) as independent predictors of inferior survival. In a similar multivariable analysis, mutant IDH1 was the only variable associated with shortened leukemia-free survival (P=0.001; hazard ration 7.0, 95% confidence interval 2.3-20.8). The presence of IDH2R140Q did not affect the overall (P=0.54) or leukemia-free (P=0.81) survival. The current study suggests a powerful adverse prognostic effect for mutant IDH1 in MDS.
与急性髓系白血病不同，关于骨髓增生异常综合征（MDS）中异柠檬酸脱氢酶（IDH）突变的预后影响，信息有限。在本研究中，对 277 例 MDS 患者进行了检测，发现 34 例（12%）存在 IDH 突变：26 例 IDH2（均为 R140Q）和 8 例 IDH1（6 例 R132S 和 2 例 R132C）。在环形铁幼粒细胞性难治性贫血中突变频率为 4%（2/56），难治性血细胞减少伴多系发育异常为 12%（16/130），无法分类的 MDS 为 14%（2/14），难治性贫血伴原始细胞过多（RAEB）-1 为 14%（6/42），RAEB-2 为 23%（8/35）。除 1 例 IDH1 突变病例和 13 例 IDH2 突变病例外，其余病例均为正常核型。多变量分析确定存在突变型 IDH1（P=0.0004；危险比 4.0，95%置信区间 1.9-8.8）、修订后的国际预后评分系统风险类别（P<0.0001）和红细胞输注需求（P=0.002）是生存不良的独立预测因素。在类似的多变量分析中，突变型 IDH1 是唯一与白血病无复发生存缩短相关的变量（P=0.001；危险比 7.0，95%置信区间 2.3-20.8）。IDH2R140Q 的存在并不影响总体（P=0.54）或白血病无复发生存（P=0.81）。本研究表明，IDH1 突变在 MDS 中具有强大的不良预后作用。
