MiRNA in adult T-cell leukemia/lymphoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE28626 | GEO | 2014/04/12
SECONDARY ACCESSION(S): PRJNA138733
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA expression was investigated in ATLL samples and in normal CD4 T-cells (resting and in vitro-stimulated). Total RNA was isolated from ATLL samples and normal T-cell controls. miRNA expression was measured using Agilent miRNA arrays.
2014-04-12 | E-GEOD-28626 | biostudies-arrayexpress
Project description:Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare subtype of ATLL harboring human T cell lymphotropic virus type-1-infected Hodgkin-Reed-Sternberg (HRS)-like cells and small to medium CD4+ T cells, which histologically mimics classic Hodgkin lymphoma (CHL). CD30+ tumor cells or HRS cells are surrounded by CD4+ non-neoplastic T cells in a rosette-like manner in CHL. Interaction between HRS cells and surrounding CD4+ T cells is important for tumor microenvironment (TME) in CHL. Tumor microenvironment of Hodgkin-like ATLL remains unclear. Here, Digital Spatial Profiling was performed on Hodgkin-like ATLL to elucidate the interaction between HRS-like cells and CD4+ T cells in Hodgkin-like ATLL. We identified CD4+ T cells expressing co-stimulatory molecules, CD28 and inducible T cell co-stimulator (ICOS), in CD4+ T cells surrounding the HRS-like cells than in those apart from HRS-like cells. Immunohistochemistry was performed in 11 cases of Hodgkin-like ATLL, which detected distinct CD4+ T cells expressing CD28 in a rosette-like manner around HRS-like cells. HRS-like cells widely expressed CD80 and CD86, which suggested CD28-CD80/CD86 interaction was important in pathogenesis of Hodgkin-like ATLL. ICOS and immune checkpoint molecules, including T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed death-1 (PD-1) were also variably expressed in CD4+ T cells surrounding HRS-like cells. Our findings provide new insights into the tumor microenvironment of Hodgkin-like ATLL and implicate a new therapeutic strategy targeting these molecules.
2023-12-06 | GSE213461 | GEO
Project description:Adult T-cell leukemia-lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from 9 patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon alpha (IFN). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2 and LMO2, with confirmation of LMO2 expression confirmed in ATLL cells at the protein level. In vivo AZT- and IFNa treatment evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycles regulated genes including those encoding ribosomal proteins. Remarkably, patients not responding to IFNa/AZT differed most from responding patients in relative over expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT-IFNa therapy may provide novel insights into the mechanisms of action in ATLL. compound_treatment_design
2010-04-12 | E-GEOD-19160 | biostudies-arrayexpress
Project description:Adult T-cell Leukemia/Lymphoma (ATLL) is a frequently incurable disease associated with the human lymphotropic virus type I (HTLV-I). The transcription factor HBZ is the only virally encoded gene that is expressed in all ATLL cases, but it is unclear why it may be essential in ATLL and how it might be targeted therapeutically. Here we performed RNA interference screening of ATLL lines and discovered that their proliferation depends on the transcription factors BATF3 and IRF4, which regulate the identity of normal immune cells. These factors, which are highly expressed in ATLL, cooperatively bind and transactivate genes that distinguish ATLL from other T cell malignancies, including BATF3 itself. HBZ binds to an ATLL-specific BATF3 super-enhancer and thereby regulates the expression of BATF3 and its downstream targets, including the oncogene MYC. The BET protein inhibitor JQ1 collapsed the transcriptional network directed by HBZ and BATF3, and was consequently toxic for ATLL lines and patient samples in vitro, and blocked growth of ATLL xenografts. Our study demonstrates that the HTLV-I virus exploits a regulatory module that can potentially be attacked therapeutically with BET protein inhibitors.
2018-07-10 | GSE94409 | GEO
Project description:Adult T-cell leukemia-lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from 9 patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon alpha (IFN). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2 and LMO2, with confirmation of LMO2 expression confirmed in ATLL cells at the protein level. In vivo AZT- and IFNa treatment evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycles regulated genes including those encoding ribosomal proteins. Remarkably, patients not responding to IFNa/AZT differed most from responding patients in relative over expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT-IFNa therapy may provide novel insights into the mechanisms of action in ATLL.
2010-04-12 | GSE19160 | GEO
Project description:CTLA4-CD28 gene fusion has been reported to occur in diverse types of T-cell lymphoma. The fusion event is expected to convert inhibitory signals to activating signals promoting proliferation and potentially transformation of T-cells. To test the function of the CTLA4-CD28 fusion gene in vivo, we generated a murine model that expresses the gene in a T-cell specific manner. The transgenic mice show shorter life spans and inflammatory responses including lymphadenopathy and splenomegaly. T-cells show higher levels of activation and infiltrate various organs including skin and lung. T-cells, in particular CD4+ helper T-cells, were also readily transplanted to immunocompromised mice. Transcriptomic profiling revealed that the gene expression pattern in CD4+ cells most closely resembles that of adult T cell leukemia/lymphoma (ATLL). Consistently, we detected supernumerary Foxp3+ cells in transgenic and transplanted mice. This is the first report demonstrating the transforming activity of the CTLA4-CD28 fusion gene in vivo, and this murine model should be useful in dissecting the molecular events subsequent to the mutation in ATLL.
2022-01-01 | GSE161035 | GEO
Project description:Adult T-cell Leukemia/Lymphoma (ATLL) is a frequently incurable disease associated with the human lymphotropic virus type I (HTLV-I). The transcription factor HBZ is the only virally encoded gene that is expressed in all ATLL cases, but it is unclear why it may be essential in ATLL and how it might be targeted therapeutically. Here we performed RNA interference screening of ATLL lines and discovered that their proliferation depends on the transcription factors BATF3 and IRF4, which regulate the identity of normal immune cells. These factors, which are highly expressed in ATLL, cooperatively bind and transactivate genes that distinguish ATLL from other T cell malignancies, including BATF3 itself. HBZ binds to an ATLL-specific BATF3 super-enhancer and thereby regulates the expression of BATF3 and its downstream targets, including the oncogene MYC. The BET protein inhibitor JQ1 collapsed the transcriptional network directed by HBZ and BATF3, and was consequently toxic for ATLL lines and patient samples in vitro, and blocked growth of ATLL xenografts. Our study demonstrates that the HTLV-I virus exploits a regulatory module that can potentially be attacked therapeutically with BET protein inhibitors.
2018-07-10 | GSE94732 | GEO
Project description:We established HTLV-1/EBV co-infected cell lines from Adult T-cell Leukemia/Lymphoma (ATLL) patients, and found that they are derived from germinal center (GC) B-cells or transitional B-cells between GC-B-cells and memory B-cells by using gene expression profiling (GEP) analysis. Expression of CD25 and TSLC1, which are diagnostic markers of ATLL cells, were identified in the ATLL-derived B-cell lines as discriminators of EBV-imortalized cell lines, indicating that HTLV-1 infection leads to express CD25 and TSLC1.
2018-09-27 | GSE87434 | GEO
Project description:In the epidermis, CCR4, CCR6, CCL20 and CCL27 were higher in ATLL than in MF. We obtained the epidermal samples from MF (n=5) and ATLL (n=5) with the aid of laser microdissection. Complementary RNA amplification were used for gene expression profiling by microarray analysis. We compaired MF with ATLL in epidermis. We obtained the epidermal dermal samples from MF (n=3) and ATLL (n=3) with the aid of laser microdissection. Complementary RNA amplification were used for gene expression profiling by microarray analysis. We compaired MF with ATLL in dermis.
2012-09-06 | E-GEOD-40639 | biostudies-arrayexpress
Project description:Transcriptional analysis of patient-derived cell lines of adult T-cell leukemia/ lymphoma (ATLL).
2022-10-01 | GSE205653 | GEO