Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival

Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to therapy and survival
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DOI:
10.1182/blood-2003-09-3243
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发表时间:
2004-04-01
期刊:
影响因子:
20.3
通讯作者:
Foa, R
Foa, R
中科院分区:
医学1区
文献类型:
--
作者:
Chiaretti, S;Li, XC;Foa, R

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检测了33例成人T细胞急性淋巴细胞白血病(T-ALL)患者的基因表达谱。非特异性筛选标准确定了313个基因在白血病细胞中的差异表达。样本的分层聚类确定了2组,反映了T细胞分化的程度,但与临床结果无关。在难治性患者和对诱导化疗有反应的患者之间进行比较,确定了一个在难治性T-ALL细胞中高度表达的单个基因,白细胞介素8(IL-8)和一组在完全缓解患者的白血病细胞中高度表达的30个基因。接下来,我们确定了19个在复发或持续完全缓解患者的T-ALL细胞中差异表达的基因。基于这些基因中的3个的表达的模型预测缓解的持续时间。3基因模型在另一组T-ALL样本上进行了验证,这些样本来自18名接受相同临床方案治疗的额外患者。这项研究表明,基因表达谱可以识别有限数量的基因,这些基因可预测成人T-ALL患者对诱导治疗的反应和缓解持续时间。(C)2004年,美国血液学会。
Gene expression profiles were examined in 33 adult patients with T-cell acute lymphocytic leukemia (T-ALL). Nonspecific filtering criteria identified 313 genes differentially expressed in the leukemic cells. Hierarchical clustering of samples identified 2 groups that reflected the degree of T-cell differentiation but was not associated with clinical outcome. Comparison between refractory patients and those who responded to induction chemotherapy identified a single gene, interleukin 8 (IL-8), that was highly expressed in refractory T-ALL cells and a set of 30 genes that was highly expressed in leukemic cells from patients who achieved complete remission. We next identified 19 genes that were differentially expressed in T-ALL cells from patients who either had a relapse or remained in continuous complete remission. A model based on the expression of 3 of these genes was predictive of duration of remission. The 3-gene model was validated on a further set of T-ALL samples from 18 additional patients treated on the same clinical protocol. This study demonstrates that gene expression profiling can identify a limited number of genes that are predictive of response to induction therapy and remission duration in adult patients with T-ALL. (C) 2004 by The American Society of Hematology.