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Chromothripsis in acute myeloid leukemia: Biological features and impact on survival.
Leukemia ( IF 11.4 ) Pub Date : 2017-Dec-18 , DOI: 10.1038/leu.2017.351
M C Fontana , G Marconi , J D M Feenstra , E Fonzi , C Papayannidis , A G L di Rorá , A Padella , V Solli , E Franchini , E Ottaviani , A Ferrari , C Baldazzi , N Testoni , I Iacobucci , S Soverini , T Haferlach , V Guadagnuolo , L Semerad , M Doubek , M Steurer , Z Racil , S Paolini , M Manfrini , M Cavo , G Simonetti , R Kralovics , G Martinelli

Chromothripsis is a one-step genome-shattering catastrophe resulting from disruption of one or few chromosomes in multiple fragments and consequent random rejoining and repair. This study define incidence of chromothripsis in 395 newly-diagnosed adult acute myeloid leukemia (AML) patients from three institutions, its impact on survival and its genomic background. SNP 6.0 or CytoscanHD Array (Affymetrix®) were performed on all samples. We detected chromothripsis with a custom algorithm in 26/395 patients. Patients harboring chromothripsis had higher age (P=0.002), ELN high risk (HR) (P<0.001), lower white blood cell (WBC) count (P=0.040), TP53 loss and/or mutations (P<0.001) while FLT3 (P=0.025) and NPM1 (P=0.032) mutations were mutually exclusive with chromothripsis. Chromothripsis-positive patients showed a worse overall survival (OS) (P<0.001) compared with HR patients (P=0.011) and a poor prognosis in a COX-HR optimal regression model. Chromothripsis presented the hallmarks of chromosome instability [i.e. TP53 alteration, 5q deletion, higher mean of copy number alteration (CNA), complex karyotype, alterations in DNA repair and cell cycle] and focal deletions on chromosomes 4, 7, 12, 16, 17. CBA. FISH showed that chromothripsis is associated with marker, derivative and ring chromosomes. In conclusion, chromothripsis frequently occurs in AML (6.6%) and influences patient prognosis and disease biology.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.351.

中文翻译:

急性髓细胞性白血病中的拟除线虫病:生物学特征及其对生存的影响。

染色体杀伤是一种因破坏多个片段中的一个或几个染色体以及随之而来的随机重新结合和修复而导致的一步一步破坏基因组的灾难。这项研究确定了来自三个机构的395名新诊断的成人急性髓细胞白血病(AML)患者的色杆菌病发病率,其对生存的影响及其基因组背景。对所有样品进行SNP 6.0或CytoscanHD Array(Affymetrix®)。我们在26/395例患者中使用自定义算法检测了色霉菌病。携带染色癣的患者年龄较大(P = 0.002),高ELN(HR)(P <0.001),白细胞(WBC)计数较低(P = 0.040),TP53丢失和/或突变(P <0.001) FLT3(P = 0.025)和NPM1(P = 0.032)突变与染色红霉病相互排斥。色菌病阳性患者表现出较差的总生存(OS)(P < 0.001)与HR患者(P = 0.011)相比,COX-HR最佳回归模型的预后较差。染色体上的毛虫病表现出染色体不稳定的特征(即TP53改变,5q缺失,更高的平均拷贝数改变(CNA),复杂的核型,DNA修复和细胞周期改变)和4、7、12、16、17号染色​​体上的局灶性缺失CBA FISH表明,色杆菌病与标记,衍生物和环状染色体有关。综上所述,嗜铬菌病常发生在AML中(6.6%),并影响患者的预后和疾病生物学。白血病在线接受文章预览,2017年12月18日。doi:10.1038 / leu.2017.351。5q缺失,更高的平均拷贝数变化(CNA),复杂的核型,DNA修复和细胞周期的变化]和4、7、12、16、17号染色​​体CBA的病灶缺失。FISH表明,色杆菌病与标记,衍生物和环状染色体有关。综上所述,嗜铬菌病常发生在AML中(6.6%),并影响患者的预后和疾病生物学。白血病在线接受文章预览,2017年12月18日。doi:10.1038 / leu.2017.351。5q缺失,更高的平均拷贝数变化(CNA),复杂的核型,DNA修复和细胞周期的变化]和4、7、12、16、17号染色​​体CBA的病灶缺失。FISH表明,色杆菌病与标记,衍生物和环状染色体有关。综上所述,嗜铬菌病常发生在AML中(6.6%),并影响患者的预后和疾病生物学。白血病在线接受文章预览,2017年12月18日。doi:10.1038 / leu.2017.351。
更新日期:2017-12-18
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