Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia.
Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia.
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急性髓样白血病中克隆特异性残留疾病的精度和预后价值。
DOI：
10.3324/haematol.2016.159681
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发表时间：
2017-07
期刊：
影响因子：
10.1
通讯作者：
Delhommeau F
中科院分区：
文献类型：
--
作者：
Hirsch P;Tang R;Abermil N;Flandrin P;Moatti H;Favale F;Suner L;Lorre F;Marzac C;Fava F;Mamez AC;Lapusan S;Isnard F;Mohty M;Legrand O;Douay L;Bilhou-Nabera C;Delhommeau F
成人急性髓系白血病(AML)的遗传图景最近被揭开。然而，由于它们的遗传异质性，目前只有少数标记被用于评估微小残留病(MRD)。最近使用多靶点策略的研究表明，在完全缓解的细胞中检测到不到5%的残留突变与更好的生存相关。在此，在一系列已知克隆结构的69个AML中，我们设计了一种基于荧光原位杂交和高灵敏度下一代测序的克隆特异性策略，分别检测后续样本中的染色体异常和突变。这些技术的结合可以跟踪缓解样本中染色体和基因组损伤，最低可达细胞总数的0.5%-0.4%。通过对69名可评估患者中65名患者的随访样本中的所有病变进行测试，我们发现启动事件通常持续存在，本身似乎是预测短期复发的不适当标记物。相比之下，在单变量和多变量分析中，缓解期样本中超过0.4%的细胞中存在两个或两个以上病变与较低的无白血病和总体生存率密切相关。虽然需要更大的前瞻性研究来扩展这些结果，但我们的数据显示，个性化、克隆特异性、MRD随访策略在绝大多数AML病例中是可行的。
The genetic landscape of adult acute myeloid leukemias (AML) has been recently unraveled. However, due to their genetic heterogeneity, only a handful of markers are currently used for the evaluation of minimal residual disease (MRD). Recent studies using multi-target strategies indicate that detection of residual mutations in less than 5% of cells in complete remission is associated with a better survival. Here, in a series of 69 AMLs with known clonal architecture, we design a clone-specific strategy based on fluorescent in situ hybridization and high-sensitivity next generation sequencing to detect chromosomal aberrations and mutations, respectively, in follow-up samples. The combination of these techniques allows tracking chromosomal and genomic lesions down to 0.5–0.4% of the cell population in remission samples. By testing all lesions in follow-up samples from 65 of 69 evaluable patients, we find that initiating events often persist and appear to be, on their own, inappropriate markers to predict short-term relapse. In contrast, the persistence of two or more lesions in more than 0.4% of the cells from remission samples is strongly associated with lower leukemia-free and overall survivals in univariate and multivariate analyses. Although larger prospective studies are needed to extend these results, our data show that a personalized, clone-specific, MRD follow up strategy is feasible in the vast majority of AML cases.
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影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
20.3
作者：
Buccisano, Francesco;Maurillo, Luca;Venditti, Adriano
通讯作者：
Venditti, Adriano
影响因子：
20.3
作者：
Jourdan, Eric;Boissel, Nicolas;Dombret, Herve
通讯作者：
Dombret, Herve
影响因子：
45.3
作者：
Chen, Yiming;Cortes, Jorge;Ravandi, Farhad
通讯作者：
Ravandi, Farhad