Molecular diagnosis of lymphoid malignancies by gene expression profiling

Molecular diagnosis of lymphoid malignancies by gene expression profiling
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DOI:
10.1097/00062752-200207000-00011
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发表时间:
2002-07-01
影响因子:
3.2
通讯作者:
Staudt, LM
Staudt, LM
中科院分区:
医学3区
文献类型:
--
作者:
Davis, RE;Staudt, LM

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利用DNA微阵列进行基因表达谱分析在提高对淋巴瘤、白血病和其他恶性肿瘤的理解、诊断和治疗方面具有巨大的潜力。弥漫性大B细胞淋巴瘤(DLBCL)的基因表达谱研究表明,这一诊断类别至少包括两种分子上不同的疾病,在分化阶段(起源细胞)、致癌机制和临床结果方面不同。基因表达谱显示,抗凋亡的NF-kappaB通路在一个DLBCL亚型,称为激活的B细胞样DLBCL中具有结构性活性,随后的研究证实,NF-kappaB是这种类型淋巴瘤的治疗靶点。对慢性淋巴细胞白血病(CLL)的DNA微阵列研究导致了一种基于基因表达的预测因子,该因子识别出两种不同的CLL亚型,它们在临床病程和CLL细胞中是否存在免疫球蛋白基因突变方面存在差异。这些发现强调了基因表达谱在确定分子和临床上不同的淋巴样恶性肿瘤亚型方面的价值,并认为这项基因组技术应该成为前瞻性临床试验的组成部分。(C)2002年Lippincott Williams Wilkins,Inc.
Gene expression profiling using DNA microarrays has great potential to improve the understanding, diagnosis, and management of lymphomas, leukemias, and other malignancies. Gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) have shown that this diagnostic category encompasses at least two molecularly distinct diseases, differing in differentiation stage (cell of origin), oncogenic mechanisms, and clinical outcome. Gene expression profiling revealed that the antiapoptotic NF-kappaB pathway is constitutively active in one DLBCL subgroup, termed activated B cell-like DLBCL, and subsequent studies validated NF-kappaB as a therapeutic target in this type of lymphoma. DNA microarray studies of chronic lymphocytic leukemia (CLL) have led to a gene expression-based predictor that identifies two subtypes of CLL that differ with respect to clinical course and presence of immunoglobulin gene mutations in the CLL cells. These findings underscore the value of gene expression profiling in defining subtypes within the lymphoid malignancies that are molecularly and clinically distinct and argue that this genomic technology should become an integral part of prospective clinical trials. (C) 2002 Lippincott Williams Wilkins, Inc.