Department of Haematology, UCL Cancer Institute, London, United Kingdom.
Blood. 2011 Jul 14;118(2):409-12. doi: 10.1182/blood-2010-12-322479. Epub 2011 May 19.
We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials. An IDH2 mutation was present in 148 cases (10%), 80% at R140 and 20% at R172. Patient characteristics and outcome differed markedly between the 2 mutations. IDH2(R140) significantly correlated with nucleophosmin mutations (NPM1(MUT)), whereas IDH2(R172) cases generally lacked other molecular mutations. An IDH2(R140) mutation was an independent favorable prognostic factor for relapse (P = .004) and overall survival (P = .008), and there was no significant heterogeneity with regard to NPM1 or FLT3 internal tandem duplication (FLT3/ITD) genotype. Relapse in FLT3/ITD(WT)NPM1(MUT)IDH2(R140) patients was lower than in favorable-risk cytogenetics patients in the same cohort (20% and 38% at 5 years, respectively). The presence of an IDH2(R172) mutation was associated with a significantly worse outcome than IDH2(R140), and relapse in FLT3/ITD(WT)NPM1(WT)IDH2(R172) patients was comparable with adverse-risk cytogenetics patients (76% and 72%, respectively).
我们调查了 IDH2 突变在 1473 例接受英国医学研究理事会 2 项临床试验治疗的年轻成年急性髓系白血病患者中的预后意义。148 例（10%）存在 IDH2 突变，80%为 R140 突变，20%为 R172 突变。两种突变的患者特征和结局明显不同。IDH2（R140）与核磷蛋白突变（NPM1（MUT））显著相关，而 IDH2（R172）病例通常缺乏其他分子突变。IDH2（R140）突变是复发（P =.004）和总生存（P =.008）的独立有利预后因素，并且与 NPM1 或 FLT3 内部串联重复（FLT3/ITD）基因型无显著异质性。FLT3/ITD（WT）NPM1（MUT）IDH2（R140）患者的复发率低于同一队列中有利风险细胞遗传学患者（分别为 5 年时的 20%和 38%）。IDH2（R172）突变的存在与明显较差的预后相关，FLT3/ITD（WT）NPM1（WT）IDH2（R172）患者的复发率与不良风险细胞遗传学患者相当（分别为 76%和 72%）。
