Adult T-cell leukemia/lymphoma (ATL) is an aggressive neoplasm immunophenotypically resembling regulatory T cells, associated with human T-cell leukemia virus type-1. Here, we performed whole-genome sequencing (WGS) of 150 ATL cases to reveal the overarching landscape of genetic alterations in ATL. We discovered frequent (33%) loss-of-function alterations preferentially targeting the CIC long isoform, which were overlooked by previous exome-centric studies of various cancer types. Long but not short isoform-specific inactivation of Cic selectively increased CD4+CD25+Foxp3+ T cells in vivo. We also found recurrent (13%) 3'-truncations of REL, which induce transcriptional upregulation and generate gain-of-function proteins. More importantly, REL truncations are also common in diffuse large B-cell lymphoma, especially in germinal center B-cell-like subtype (12%). In the non-coding genome, we identified recurrent mutations in regulatory elements, particularly splice sites, of several driver genes. In addition, we characterized the different mutational processes operative in clustered hypermutation sites within and outside immunoglobulin/T-cell receptor genes and identified the mutational enrichment at the binding sites of host and viral transcription factors, suggesting their activities in ATL. By combining the analyses for coding and noncoding mutations, structural variations, and copy number alterations, we discovered 56 recurrently altered driver genes, including 11 novel ones. Finally, ATL cases were classified into 2 molecular groups with distinct clinical and genetic characteristics based on the driver alteration profile. Our findings not only help to improve diagnostic and therapeutic strategies in ATL, but also provide insights into T-cell biology and have implications for genome-wide cancer driver discovery.
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http://dx.doi.org/10.1182/blood.2021013568 | DOI Listing |
Cardiooncology
December 2024
Department of Cardiovascular Medicine, Mayo Clinic, 200 1 St SW, Rochester, MN, 55905, USA.
Background: CD19 CAR T-cell therapy is a novel anti-cancer treatment that has produced remarkable responses in relapsed or refractory B-cell hematological malignancies. Cytokine Release Syndrome (CRS) is a dysregulated immune response that frequently occurs after CAR T-cell infusion. It can cause cardiac dysfunction and circulatory collapse negatively impacting outcomes and survival.
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December 2024
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Background: Pancreatic adenocarcinoma (PDAC) exhibits a complex microenvironment with diverse cell populations influencing patient prognosis. Single-cell RNA sequencing (scRNA-seq) was used to identify prognosis-related cell types, and DNA methylation (DNAm)-based models were developed to predict outcomes based on their cellular characteristics.
Methods: We integrated scRNA-seq, bulk data, and clinical information to identify key cell populations associated with prognosis.
Int Immunopharmacol
December 2024
Department of Immunology, Tarbiat Modares University, Tehran, Iran.
Sulfur mustard (SM) induced pulmonary disorder is a heterogeneous disease characterized by uncontrolled inflammatory immune responses. In this cross-sectional study carried out in Isfahan-Iran, our objective was to thoroughly evaluate the clinical health and peripheral blood leukocyte profiles of adult veterans exposed to SM 25-30 years. In total, 361 people were studied in two groups, 287 chemical veterans with pulmonary complications and 64 healthy individuals as a control group.
View Article and Find Full Text PDFGeroscience
December 2024
Department of Pharmacology & Nutritional Sciences, Diabetes and Obesity Research Priority Area, University of Kentucky, Lexington, KY, USA.
Cancer Immunol Immunother
December 2024
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Synovial sarcoma is an aggressive soft-tissue cancer that shows limited responses to current immunotherapeutic approaches using immune checkpoint blockade or adoptive cell therapy. To improve immunotherapy for this cancer, understanding how the immune cells in the tumor microenvironment associate with histological subtype, disease progression and current therapies is vital. To evaluate the immune infiltrate in synovial sarcoma in relation to histological subtype, disease progression and in response to cytotoxic treatment, we performed immunodetection of T cells, CD68 myeloid cells, endothelial cells and keratin on a series of 41 synovial sarcoma patients at various stages of disease.
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