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通过基于芯片的比较基因组杂交技术鉴定急性髓系白血病中具有临床重要性的染色体畸变

Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization.

作者信息

Mehrotra Meenakshi, Luthra Rajyalakshmi, Ravandi Farhad, Sargent Rachel L, Barkoh Bedia A, Abraham Ronald, Mishra Bal Mukund, Medeiros L Jeffrey, Patel Keyur P

机构信息

Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center , Houston, TX , USA.

出版信息

Leuk Lymphoma. 2014 Nov;55(11):2538-48. doi: 10.3109/10428194.2014.883073.

DOI:10.3109/10428194.2014.883073
PMID:24446873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4110186/
Abstract

Array-based comparative genomic hybridization (aCGH) chromosomal analysis facilitates rapid detection of cytogenetic abnormalities previously undetectable by conventional cytogenetics. In this study, we analyzed 48 uniformly treated patients with acute myeloid leukemia (AML) by 44K aCGH and correlated the findings with clinical outcome. aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb minimally deleted region on chromosome 5 lies between 5q14.3 and 5q33.3 and contains 634 genes and 15 microRNAs, whereas loss of chromosome 17 spans 3194 kb and involves 342 genes and 12 microRNAs. Loss of a 155 kb region on 5q33.3 (p < 0.05) was associated with achievement of complete remission (CR). In contrast, loss of 17p11.2-q11.1 was associated with a lower CR rate and poorer overall survival (Kaplan-Meier analysis, p < 0.0096). aCGH detected loss of 17p in 12/48 patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH analysis adds to the prognostic stratification of patients with AML.

摘要

基于芯片的比较基因组杂交（aCGH）染色体分析有助于快速检测以往常规细胞遗传学方法无法检测到的细胞遗传学异常。在本研究中，我们采用44K aCGH对48例接受统一治疗的急性髓系白血病（AML）患者进行了分析，并将结果与临床结局相关联。aCGH识别出了目前意义不明、小至5 kb的先前未检测到的畸变。5号染色体上36.7 Mb的最小缺失区域位于5q14.3和5q33.3之间，包含634个基因和15个微小RNA，而17号染色体缺失跨度为3194 kb，涉及342个基因和12个微小RNA。5q33.3上一个155 kb区域的缺失（p<0.05）与完全缓解（CR）的实现相关。相比之下，17p11.2 - q11.1的缺失与较低的CR率和较差的总生存期相关（Kaplan - Meier分析，p<0.0096）。与传统核型分析在48例患者中检测到9例17p缺失相比，aCGH在48例患者中检测到12例17p缺失。总之，aCGH分析有助于AML患者的预后分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/4110186/dbf94e73bbcf/nihms596168f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/4110186/dbf94e73bbcf/nihms596168f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/4110186/d6802efe4e52/nihms596168f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/4110186/a36cdeb2575f/nihms596168f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/740b/4110186/dbf94e73bbcf/nihms596168f5.jpg

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