A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia.
A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia.
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DOI：
10.18632/oncotarget.4113
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发表时间：
2015-06-30
期刊：
影响因子：
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通讯作者：
Rousseaux S
中科院分区：
文献类型：
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作者：
Wang J;Mi JQ;Debernardi A;Vitte AL;Emadali A;Meyer JA;Charmpi K;Ycart B;Callanan MB;Carroll WL;Khochbin S;Rousseaux S
癌症中的异常基因表达代表了癌症标志物和治疗靶点的未充分探索的来源。为了识别与急性淋巴细胞白血病（ALL）生存相关的基因表达特征，设计了一种搜索异常基因活性的策略，该策略包括将几种过滤器应用于两项儿科ALL研究的转录组数据集。在白血病原始细胞中的表达与预后相关的六个基因被确定：三个预测不良预后的基因（AK022211，FASTKD 1和STARD 4）和三个与良好预后相关的基因（CAMSAP 1，PCGF 6和SH3RF 3）。结合这6个基因的表达不仅可以成功预测两项儿童ALL研究的预后，还可以预测两个独立的成人患者验证队列的预后，一个来自公开研究，另一个由62名新招募的中国患者组成。此外，我们的数据表明，我们的六个基因为基础的测试是特别有效的分层MLL或BCR，ABL阴性患者。最后，发现了儿童和成人ALL侵袭性形式的共同生物学特征，包括休眠造血干细胞的特征，提示了新的治疗策略。
Abnormal gene expression in cancer represents an under-explored source of cancer markers and therapeutic targets. In order to identify gene expression signatures associated with survival in acute lymphoblastic leukemia (ALL), a strategy was designed to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Combining the expression of these 6 genes could successfully predict prognosis not only in the two discovery pediatric ALL studies, but also in two independent validation cohorts of adult patients, one from a publicly available study and one consisting of 62 newly recruited Chinese patients. Moreover, our data demonstrate that our six gene based test is particularly efficient in stratifying MLL or BCR.ABL negative patients. Finally, common biological traits characterizing aggressive forms of ALL in both children and adults were found, including features of dormant hematopoietic stem cells, suggesting new therapeutic strategies.