Dataset Information

Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.

ABSTRACT: Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.

SUBMITTER: Yamagishi M

PROVIDER: S-EPMC8355240 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.

Yamagishi Makoto M Kubokawa Miyuki M Kuze Yuta Y Suzuki Ayako A Yokomizo Akari A Kobayashi Seiichiro S Nakashima Makoto M Makiyama Junya J Iwanaga Masako M Fukuda Takahiro T Watanabe Toshiki T Suzuki Yutaka Y Uchimaru Kaoru K

Nature communications 20210810 1

Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset in ...[more]

PMID: 34376672

Similar Datasets

Project description:Adult T cell leukemia-lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-I) retrovirus. ATL carries a dismal prognosis. ATL classifies into four subtypes (acute, lymphoma, chronic, and smoldering) which display different clinical features, prognosis and response to therapy, hence requiring different clinical management. Smoldering and chronic subtypes respond well to antiretroviral therapy using the combination of zidovudine (AZT) and interferon-alpha (IFN) with a significant prolongation of survival. Conversely, the watch and wait strategy or chemotherapy for these indolent subtypes allies with a poor long-term outcome. Acute ATL is associated with chemo-resistance and dismal prognosis. Lymphoma subtypes respond better to intensive chemotherapy but survival remains poor. Allogeneic hematopoietic stem cell transplantation (HSCT) results in long-term survival in roughly one third of transplanted patients but only a small percentage of patients can make it to transplant. Overall, current treatments of aggressive ATL are not satisfactory. Prognosis of refractory or relapsed patients is dismal with some encouraging results when using lenalidomide or mogamulizumab. To overcome resistance and prevent relapse, preclinical or pilot clinical studies using targeted therapies such as arsenic/IFN, monoclonal antibodies, epigenetic therapies are promising but warrant further clinical investigation. Anti-ATL vaccines including Tax peptide-pulsed dendritic cells, induced Tax-specific CTL responses in ATL patients. Finally, based on the progress in understanding the pathophysiology of ATL, and the risk-adapted treatment approaches to different ATL subtypes, treatment strategies of ATL should take into account the host immune responses and the host microenvironment including HTLV-1 infected non-malignant cells. Herein, we will provide a summary of novel treatments of ATL in vitro, in vivo, and in early clinical trials.

Dataset Information

Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.

Publications

Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets