Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. Copy number analysis of Affymetrix 50K SNP arrays was performed for leukemic cell samples from10 acute-type ATL patients.
Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients. The breakpoints accumulated frequently adjacent to the T cell receptor alpha/delta chain locus (TCRα/δ) with chromosomal deletions at 14q11 and a recurrent 0.9 Mb interstitial deletion was identified at a region including part of the TCRα/δ locus. Because leukemia-associated genes are frequently located near the breakpoint cluster regions, we then analyzed the gene expression profiles of ATL cells and identified N-myc downstream regulated gene 2 (NDRG2) as one of the genes that are down-regulated in ATLL cells among the 25 genes mapped to the region adjacent to the recurrently deleted regions at 14q11. We compared the gene expression profiles of ATL cells from seven acute-type ATL patients and CD4+ T lymphocytes from the peripheral blood of five healthy volunteers as references using oligonucleotide microarrays.
Project description:Genomic aberration profiles of chronic type adult T-cell leuekemia/lymphoma (ATL) and acute type ATL(clinical samples) . The Cy3-labeled normal control DNA was obtained from peripheral blood mononuclear cells of healthy males.
Project description:It has been known that aberrant isoforms of Ikaros family ptoteins are expressed in malignant cells. We identified that PBMC of ATL (acute T-cell leukemia) patients expresses different patterns of Helios isoforms compared with normal PBMC. In order to investigate the biological impact of ATL-type Helios isoform, we conducted complehensive gene expression analyses in Jurkat cells overexpressing ATL-type Helios. Also, we investigated the influence of WT-Helios or WT-Ikaros knockdown on the gene expression profile and compared with that of the cells with ATL-type Helios overexpression.
Project description:Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive and fatal disease. We have examined 18 ATL patient samples using Affymetrix HG-U133A2.0 arrays. Using the BRB array program, we identified genes differentially expressed in leukemia cells compared to normal lymphocytes. Several unique genes were identified that were overexpressed in leukemia cells including TNFSF11, RGS13, MAFb, CSPG2, C/EBPalpha and TCF4. 200 of the most highly overexpressed ATL genes were analyzed by the PathwayStudio 4.0 program. ATL leukemia cells were characterized by an increase in genes linked to "central" genes CDC2/cyclin B1, SYK/LYN, PCNA and BIRC5. Because of its potential therapeutic importance, we focused our studies on the regulation and function of BIRC5, whose expression was increased in 13 of 14 leukemia samples. TCF4 reporter assays and transfection of DN-TCF4 demonstrated that TCF4 regulates BIRC5 gene expression. Functionally, transfection of ATL cells wi BIRC5 shRNA decreased BIRC5 exprression and cell viability 80%. Clinical treatment of ATL patients with Zenapax or bortezomib decreased BIRC5 expression and cell viability. These experiments represent the first direct experimental evidence that BIRC5 plays an important role in ATL cell viability and provides important insight into ATL genesis and potential targeted therapies. Experiment Overall Design: Gene expression profiles of 7 control and 18 ATL patient samples were analyzed using Affymetrix HG-U133A2.0 arrays.
Project description:It has been known that aberrant isoforms of Ikaros family ptoteins are expressed in malignant cells. We identified that PBMC of ATL (acute T-cell leukemia) patients expresses different patterns of Helios isoforms compared with normal PBMC. In order to investigate the biological impact of ATL-type Helios isoform, we conducted complehensive gene expression analyses in Jurkat cells overexpressing ATL-type Helios. Also, we investigated the influence of WT-Helios or WT-Ikaros knockdown on the gene expression profile and compared with that of the cells with ATL-type Helios overexpression. Total RNA samples from Jurkat cells were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.
Project description:Comprehensive gene expression profiles of thirteen samples of chronic type ATL and twenty one samples of acute type ATL were analyzed to detect tumor-specific genes. We studied a total of 34 adult T-cell leuekmia/lymphoma cases, whose samples and clinical data were available.
Project description:We recently mapped 605 chromosomal breakpoints in 61 ATL cases by spectral karyotyping and identified chromosome 14q11 as one of the most common chromosomal breakpoint regions. To map the precise location of chromosomal breakpoints at 14q11, we performed single-nucleotide polymorphism (SNP)-based comparative genomic hybridization on leukemia cells from acute-type ATL patients.
Project description:Adult T-cell Leukemia (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes, associated with retrovirus human T-cell leukemia virus type I (HTLV-1). To elucidate the complex molecular mechanism of anti-Growth effect of the HIV integrase inhibitor, MK-2048 in ATL cells, we attempted to perform gene expression profiling.