Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.
Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH.
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DOI：
10.1371/journal.pone.0016623
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发表时间：
2011-02-14
期刊：
影响因子：
3.7
通讯作者：
Bernheim A
中科院分区：
文献类型：
--
作者：
Itzhar N;Dessen P;Toujani S;Auger N;Preudhomme C;Richon C;Lazar V;Saada V;Bennaceur A;Bourhis JH;de Botton S;Bernheim A
治疗相关性急性白血病（t-AML）是用于原发性癌症治疗的细胞毒性治疗的严重并发症。与新发急性白血病（p-AML）患者相比，这些患者的结局较差。t-AML中的细胞遗传学异常与p-AML中发现的细胞遗传学异常相似，但根据诱导剂的不同，存在更常见的不利核型。在烷化剂后观察到5号或7号染色体的丢失，而在拓扑异构酶II抑制剂后发现平衡易位。本研究使用高分辨率阵列CGH比较了t-AML和p-AML，以便以比常规细胞遗传学更高的分辨率发现拷贝数异常（CNA）。在30例t-AML中观察到的CNA多于36例p-AML：在t-AML中观察到104例CNA，其中63例丢失，41例获得（每例平均数为3.46），而在p-AML中观察到69例CNA，其中32例丢失，37例获得（每例平均数为1.9）。在具有先前“正常”核型的原发性白血病中，18%表现出先前未检测到的CNA，而在具有正常核型的（少数）t-AML中，该比率为50%。在t-AML和p-AML中发现了几个最小关键区域（MCR）。两组均未发现共同的MCR。在t-AML中，40 kb缺失的MCR指向21 q22上的RUNX 1，该基因编码与白血病和家族性血小板减少症的频繁重排有关的转录因子。在初治AML中，从具有复杂aCGH谱的患者中观察到1 Mb MCR携带ERG和ETS 2。通过aCGH和已经发表的类似技术获得的高分辨率细胞基因组学使我们能够表征许多非随机染色体异常。这项工作支持了以下假设：它们可以分为几类：所有AML常见的异常;在t-AML中更常见的异常和在p-AML中特别发现的异常。
Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA) at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case) in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case). In primary leukemia with a previously “normal” karyotype, 18% exhibited a previously undetected CNA, whereas in the (few) t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs) were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML.
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影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
3.2
作者：
Gao, Mengya;Liu, Qi;Wu, Qiong
通讯作者：
Wu, Qiong
影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
20.3
作者：
Christiansen, DH;Andersen, MK;Pedersen-Bjergaard, J
通讯作者：
Pedersen-Bjergaard, J
影响因子：
4.5
作者：
Grozdanov, Petar N.;Roy, Sujayita;Meier, U. Thomas
通讯作者：
Meier, U. Thomas