Whole-genome landscape of adult T-cell leukemia/lymphoma
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ABSTRACT:
PROVIDER: EGAS00001005237 | EGA |
REPOSITORIES: EGA
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Project description:Whole-genome sequence (WGS) data of tumor-normal pairs from 139 ATL patients and RNA sequence (RNA-seq) data of tumors from 28 ATL patients.
| EGAD00001008289 | EGA
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.
2009-02-08 | E-GEOD-14317 | biostudies-arrayexpress
Project description:Spontaneous remission in patients with various cancers has been reported. Some patients with adult T-cell leukemia–lymphoma (ATL) have experienced spontaneous remission, although the mechanisms for this remain unknown. In this study, we analyzed ATL cells and human T-cell leukemia virus type 1 (HTLV-1)- infected cells using cytometry by time-of-flight mass spectrometry. We observed a small number (less than 5% on average) of ATL cells and HTLV-1–infected cells that expressed CD14 and other dendritic cell (DC)-associated molecules such as CD1c, CD11b, CD11c, and CD141. Single-cell analysis revealed that these T cells expressing DC markers also contained rearranged T-cell receptor genes, indicating that these cells are indeed derived from T cells. In a patient with ATL who entered remission after contracting coronavirus disease 2019, the number of DC-like T cells increased, and an enzyme-linked immunosorbent spot assay detected CTLs against the Tax protein in accordance with a regression of ATL. These findings suggest that DC-like ATL cells acquire antigen-presenting capability and induce spontaneous remission through enhanced immunity to the virus. Specifically, in an ATL cell line, enforced expression of IRF8 and PU.1, in addition to endogenous BATF3 expression, increased CD86 expression and enabled the cells to present Tax peptide antigens to T cells. Collectively, these data indicate that ATL cells acquire antigen-presenting activity when IRF8, PU.1, and BATF3 are expressed, suggesting that the transition of a subset of T cells to DC-like T cells can induce immune responses to viral antigens, resulting in spontaneous remission. Thus, the transition of T cells to DC-like T cells is a unique mechanism for spontaneous remission in ATL.
2025-04-16 | GSE294224 | GEO
Project description:To identify chromosomal alterations in ATL, SNP array analyses were performed in 19 leukemia cell samples from ATL patients and 9 ATL-related cell lines. ATL displayed complex chromosomal abnormalities, but it contained recurrent chromosomal amplification and deletion, including 14q11 and 14q32, which may be associated with the development of ATL. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved peripheral blood samples and from cell line samples.
2017-06-06 | GSE99667 | GEO
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive miRNA expression profiling in 40 ATL patients and in 22 healthy volunteers. Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by miRNA expression microarray analyses.
2012-02-23 | E-GEOD-31629 | biostudies-arrayexpress
Project description:Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes. In this study, we performed RNA-sequencing (RNA-seq) analysis for ATL samples including 9 primary tumors and 1 ATL cell line to clarify gene expression profiles in this disease.
| EGAS00001003575 | EGA
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.
2014-02-01 | E-MTAB-1808 | biostudies-arrayexpress
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive gene expression profiling in 52 ATL patients and in 21 healthy volunteers. Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by human whole genome gene expression microarray analyses.
2012-02-23 | E-GEOD-33615 | biostudies-arrayexpress
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.
2012-12-20 | E-GEOD-43017 | biostudies-arrayexpress
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.
2014-01-31 | E-GEOD-54509 | biostudies-arrayexpress