Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine.
Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine.
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DOI：
10.1038/bcj.2013.52
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发表时间：
2013-11-01
影响因子：
12.8
通讯作者：
Raynaud, S.
中科院分区：
文献类型：
--
作者：
Cluzeau, T.;Moreilhon, C.;Mounier, N.;Karsenti, J-M;Gastaud, L.;Garnier, G.;Re, D.;Montagne, N.;Gutnecht, J.;Auberger, P.;Fuzibet, J. G.;Cassuto, J-P;Raynaud, S.
中期细胞遗传学(MC)在骨髓增生异常综合征(MDSS)患者的风险分层中起着重要作用，并可影响治疗的选择。阿扎替丁(AZA)改变了MDS或不适合强化化疗的急性髓系白血病(AML)患者的预后。没有AZA益处的患者的识别将允许AZA联合或其他药物作为一线治疗。新的全基因组扫描技术，如基于单核苷酸多态性微阵列(SNP-A)的分子核型分析(MK)，改善了MDS和AML的风险分层。在风险较低的MDS患者中，基因组完整性的维持不到三兆碱基(MB)基因组的完全破坏与更好的总体生存(OS)相关。在这项SNP-A研究中，我们旨在为51名接受AZA治疗的高危MDS/AML患者中影响中位OS的基因组拷贝数(CN)改变(TGA)确定一个截断值。我们观察到，根据基于SNP-A的MK(分别为8个月和15个月，P=0.02)，TGA的-GT；100 Mb增加了OS恶化的相对风险。我们的数据表明，TGA的精确测量可以为接受AZA治疗的较差和非常差的修订国际预后评分系统(IPSS-R)患者提供预测性信息。
Metaphase cytogenetics (MC) has a major role in the risk stratification of patients with myelodysplastic syndromes (MDSs) and can affect the choice of therapies. Azacitidine (AZA) has changed the outcome of patients with MDS or acute myeloid leukemia (AML) unfit for intensive chemotherapy. Identification of patients without the benefit of AZA would allow AZA combination or other drugs in first-line treatments. New whole-genome scanning technologies such as single nucleotide polymorphism microarray (SNP-A)-based molecular karyotyping (MK) improve the risk stratification in MDS and AML. Maintenance of genomic integrity is less than three megabases (Mbs) total disruption of the genome correlated with better overall survival (OS) in patients with lower-risk MDS. In this SNP-A study, we aimed at defining a cutoff value for total genomic copy number (CN) alterations (TGA) influencing the median OS in a cohort of 51 higher-risk MDS/AML patients treated with AZA. We observed that the relative risk of worse OS increased >100 Mb of TGA, as detected by SNP-A-based MK (8 and 15 months respectively, P=0.02). Our data suggest that precise measurement of TGA could provide predictive information in poor and very poor revised International Prognostic Scoring system (IPSS-R) patients treated with AZA.
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