Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes
Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes
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DOI：
10.1182/blood-2006-06-028969
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发表时间：
2007-03-01
期刊：
影响因子：
20.3
通讯作者：
Delsol, Georges
中科院分区：
文献类型：
--
作者：
Lamant, Laurence;De Reynies, Aurelien;Delsol, Georges
利用微阵列基因表达谱，我们分析了一个同质系列的32例系统性间变性大细胞淋巴瘤（ALCL）和5 ALCL细胞系。无监督分析将ALCL分为2个簇，基本上对应于形态亚组（即常见型、小细胞型和“混合”变体）和临床变量。ALCL形态学变异的患者为晚期疾病。该组包括大量经历早期复发的患者。监督分析显示ALK（+）ALCL和ALK（-）ALCL具有不同的基因表达谱，进一步证实它们是不同的实体。在ALK（+）和ALK（-）样本之间最显著差异表达的基因中，我们发现BCL 6、PTPN 12、CEBPB和SERPINA 1基因在ALK（+）ALCL中过表达。这一结果通过组织微阵列在BCL-6、C/EBP β和serpinA 1的蛋白水平得到证实。ALK（-）ALCL的分子特征包括CCR 7、CNTFR、IL 22和IL 21基因的过表达，但未提供该肿瘤亚型的分子机制的任何明显线索。一旦在大量患者中得到证实，本研究的结果可用于诊断时患者的临床和治疗管理。
With the use of microarray gene-expression profiling, we analyzed a homogeneous series of 32 patients with systemic anaplastic large-cell lymphoma (ALCL) and 5 ALCL cell lines. Unsupervised analysis classified ALCL in 2 clusters, corresponding essentially to morphologic subgroups (ie, common type vs small cell and "mixed" variants) and clinical variables. Patients with a morphologic variant of ALCL had advanced-stage disease. This group included a significant number of patients who experienced early relapse. Supervised analysis showed that ALK(+) ALCL and ALK(-) ALCL have different gene-expression profiles, further confirming that they are different entities. Among the most significantly differentially expressed genes between ALK(+) and ALK(-) samples, we found BCL6, PTPN12, CEBPB, and SERPINA1 genes to be overexpressed in ALK(+) ALCL. This result was confirmed at the protein level for BCL-6, C/EBP beta and serpinA1 through tissue microarrays. The molecular signature of ALK(-) ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype. Once confirmed on a larger number of patients, the results of the present study could be used for clinical and therapeutic management of patients at the time of diagnosis.