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)是一种临床表现多样的外周T淋巴细胞恶性肿瘤，与人类T淋巴细胞病毒1型(HTLV-1)相关。然而，ATL多步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的表达变化，采用高密度寡核苷酸芯片(HuGeneFL，Affymetrix，Santa Clara，CA)，比较了4对新鲜ATL细胞(3例慢性期进展到急性期，典型慢性期和典型急性期)的基因表达谱。与慢性期样本相比，我们确定了203个普遍上调的基因(包括核糖体蛋白、蛋白质体亚单位、真核翻译因子、免疫亲和素、热休克蛋白和对DNA复制至关重要的基因，如解旋酶)和91个通常下调的基因(包括免疫分子和磷酸酶)。此前已确定其中几个基因与HTLV-1的Tax蛋白有关。在相应的慢性/急性ATL样本中，一些上调的基因位于比较基因组杂交确定的扩增区域。相比之下，下调的基因都不位于缺失区域。利用实时定量聚合酶链式反应，我们确认了微阵列的结果-在另外32个ATL-样本中分析和观察到了类似的基因表达变化。这些结果表明，在ATL从慢性期到急性期的转变过程中，一组独特的已知在细胞转化和/或激活中起关键作用的基因受到调节。

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.