|Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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.