Antherieu Gabriel, Bidet Audrey, Huet Sarah, Hayette Sandrine, Migeon Marina, Boureau Lisa, Sujobert Pierre, Thomas Xavier, Ghesquières Hervé, Pigneux Arnaud, Heiblig Mael
Department of Hematology, Lyon-Sud Hospital, Hospices Civils de Lyon, 69495 Pierre Bénite, France.
Hematology Biology, Molecular Hematology, Bordeaux University Hospital, 33600 Pessac, France.
Cancers (Basel). 2021 May 10;13(9):2272. doi: 10.3390/cancers13092272.
Recently, a new subset of acute myeloid leukemia (AML) presenting a direct partial tandem duplication (PTD) of the gene was described. The consequences of this alteration in terms of outcome and response to treatment remain unclear. We analyzed retrospectively a cohort of -mutated patients with newly diagnosed AML. With a median follow-up of 3.6 years, the median overall survival was 12.1 months. -mutated patients were highly enriched in mutations affecting epigenetic actors and the signaling pathway. Integrating in ELN classification abrogates its predictive value on survival suggesting that this mutation may overcome other genomic marker effects. In patients receiving intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) significantly improved the outcome compared to non-transplanted patients. In the multivariate analysis, only HSCT at any time in complete remission (HR = 2.35; = 0.034) and status (HR = 0.29; = 0.014) were independent variables associated with overall survival, whereas age was not. In conclusion, our results emphasize that should be considered as a potential adverse prognostic factor. However, as -mutated patients are usually considered an intermediate risk group, upfront HSCT should be considered in first CR due to the high relapse rate observed in this subset of patients.
最近,描述了一种新的急性髓系白血病(AML)亚型,其存在该基因的直接部分串联重复(PTD)。这种改变对预后和治疗反应的影响仍不清楚。我们回顾性分析了一组新诊断的AML患者队列,这些患者存在该基因突变。中位随访3.6年,中位总生存期为12.1个月。该基因突变的患者中,影响表观遗传因子和该信号通路的突变高度富集。将该基因突变纳入欧洲白血病网络(ELN)分类会消除其对生存的预测价值,这表明该突变可能会克服其他基因组标志物的影响。在接受强化化疗的患者中,与未接受造血干细胞移植(HSCT)的患者相比,HSCT显著改善了预后。在多变量分析中,仅完全缓解期任何时间的HSCT(风险比[HR]=2.35;P=0.034)和该基因突变状态(HR=0.29;P=0.014)是与总生存期相关的独立变量,而年龄不是。总之,我们的结果强调该基因突变应被视为潜在的不良预后因素。然而,由于该基因突变的患者通常被视为中危组,鉴于在这一患者亚组中观察到的高复发率,首次完全缓解时应考虑早期进行HSCT。