Identifying progression-specific genes in adult T-cell leukemia/lymphoma by using oligonucleotide microarrays.

使用寡核苷酸微阵列识别成人 T 细胞白血病/淋巴瘤的进展特异性基因。

• 批准号: 13671068
• 负责人: TSUKASAKI Kunihiro
• 金额: $ 2.56万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671068/
• 关键词: adult T-cell leukemia; lymphoma; human T-lymphotropic virus type-1; multi-step carcinogenesis; expression profile; comprehensive analysis; micro-array

Adult T-cell leukemia/lymphoma (ATL), i.e., peripheral T-lymphocytic malignancy with diverse clinical features, is associated with human T-lymphotropic virus type-1 (HTLV-1). However, the precise mechanism of multi-step leukemogenesis in ATL remains unknown. To understand the change in expression that occur in the progression from chronic phase to acute crisis of ATL, the gene expression profiles of fresh ATL cells were compared in 4 pairs of samples (progression of chronic to acute- phase in 3 patients, and typical chronic phase sample versus typical acute phase sample) using high density oligonucleotide microarrays (HuGeneFL, Affymetrix, Santa Clara, CA). We identified 203 genes that were commonly up-regulated (including ribosomal proteins, proteosome subunits, eukaryotic translation factors, immunophilins, heat shock proteins and genes important for DNA replication, such as helicase) and 91 genes that were commonly down-regulated (including immune molecules and a phosphatase) in the acute phase as compared to chronic phase samples. Several of the genes were previously identified to be associated with the Tax protein of HTLV-1. Some of the up-regulated genes were located in an amplified regions identified as determined by comparative genomic hybridization in the corresponding chronic/acute ATL sample. In contrast, none of the down-regulated genes were located in deleted regions. Using real-time quantitative polymerase chain reaction, we confirmed the microarray-results in those specimens analyzed and observed similar changes in gene expression in 32 additional ATL-specimens. These results demonstrated that a distinct set of genes that are known to be critical in cell transformation and/or activation are modulated during the transition from the chronic to the acute phase of ATL.

成人 T 细胞白血病/淋巴瘤 (ATL)，即具有不同临床特征的外周 T 淋巴细胞恶性肿瘤，与人类 T 淋巴细胞病毒 1 型 (HTLV-1) 有关。然而，ATL 多步骤白血病发生的确切机制仍不清楚。为了了解 ATL 从慢性期进展到急性危象过程中发生的表达变化，使用高密度寡核苷酸微阵列（HuGeneFL，Affymetrix，Santa Clara，CA）比较了 4 对样本（3 名患者的慢性期进展为急性期，以及典型慢性期样本与典型急性期样本）中新鲜 ATL 细胞的基因表达谱。与慢性期样本相比，我们鉴定了 203 个在急性期通常上调的基因（包括核糖体蛋白、蛋白体亚基、真核翻译因子、亲免素、热休克蛋白和对 DNA 复制重要的基因，如解旋酶）和 91 个通常下调的基因（包括免疫分子和磷酸酶）。先前已鉴定出其中几个基因与 HTLV-1 的 Tax 蛋白相关。一些上调基因位于通过相应慢性/急性 ATL 样本中的比较基因组杂交确定的扩增区域中。相反，没有一个下调基因位于删除区域。使用实时定量聚合酶链式反应，我们确认了所分析样本中的微阵列结果，并在另外 32 个 ATL 样本中观察到了类似的基因表达变化。这些结果证明，在 ATL 从慢性期向急性期的转变过程中，一组已知对细胞转化和/或激活至关重要的独特基因受到调节。