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

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嗜T淋巴细胞病毒1型（HTLV-1）相关。然而，ATL中多步骤白血病发生的确切机制仍不清楚。为了理解在ATL从慢性期到急性危象的进展中发生的表达变化，使用高密度寡核苷酸微阵列（HuGeneFL，Affytelum，Santa Clara，CA）在4对样品中比较新鲜ATL细胞的基因表达谱（3名患者的慢性期到急性期的进展，以及典型的慢性期样品与典型的急性期样品）。我们确定了203个基因，通常上调（包括核糖体蛋白，蛋白体亚基，真核生物翻译因子，亲免疫素，热休克蛋白和基因的DNA复制，如解旋酶的重要）和91个基因，通常下调（包括免疫分子和磷酸酶）在急性期相比，慢性期样品。其中几个基因先前被鉴定为与HTLV-1的Tax蛋白相关。一些上调的基因位于扩增的区域中，如通过相应的慢性/急性ATL样品中的比较基因组杂交所确定的。相反，没有一个下调的基因位于缺失区域。使用实时定量聚合酶链反应，我们证实了微阵列的结果，在这些标本中分析，并观察到类似的变化，在另外32个ATL标本的基因表达。这些结果表明，在ATL从慢性期到急性期的过渡期间，已知在细胞转化和/或活化中至关重要的一组不同的基因受到调节。

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.