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An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing

ABSTRACT: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing

PROVIDER: PRJNA918588 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22984657_1.fastq.gz	Fastqsanger.gz
	SRR22984657_2.fastq.gz	Fastqsanger.gz
	SRR22984658_1.fastq.gz	Fastqsanger.gz
	SRR22984658_2.fastq.gz	Fastqsanger.gz
	SRR22984659_1.fastq.gz	Fastqsanger.gz

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An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing

Project description:T cell lymphomas (TCL) contains a group of heterogeneous non-Hodgkin lymphomas (NHL) with T cell origins. Therapy responses and outcomes remain poor for patients with TCL due to the absence of TCL-specific regimens 1,2. In addition, TCL is highly heterogenous and contains over 40 subtypes according to 2022 WHO classification 3, making the diagnosis and treatment more challenging. In this study, by using single cell technology, we reported a patient with a previously unreported TCL subtype, which was featured by a unique TCR presentations (co-expressing of two a chains, one b chain and one g chain). We deeply dissected the molecular signatures of this unique TCL subtype to better understand the disease biology and molecular pathogenesis, which can also accelerate the development of novel diagnosis and treatment strategies.

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Case Report: An unclassified T cell lymphoma subtype with co-expression of TCR αβ and γ chains revealed by single cell sequencing.

Project description:BackgroundT cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell.Case presentationA 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient's PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38.ConclusionsWe identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype.

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