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Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越:重点期刊

机构: [1]Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [2]Beijing Advaneed Inn ovati on Cen ter for Big Data-Based Precisi on Medicine, Beihang University and Capital Medical Un iversity, Beijing Tongren Hospital, Beijing 100730, China [3]Nanning Life-Ontology Biotechnology Co., Ltd., Nanning 530000, China [4]Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China
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关键词: Cell heterogeneity immune escape mantle cell lymphoma multidrug resistance scRNA-seq

摘要:
Objective: Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with high heterogeneity and a high recurrence rate. How heterogenous cell populations contribute to relapse remains to be elucidated. Methods: We performed single cell RNA sequencing (scRNA-seq) on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL. We identified 10 subpopulations comprising 4 malignant B cell subtypes, 3 T cell subtypes, 2 dendritic cell subtypes and 1 natural killer (NK) cell subtype. Subsequently, we identified cell markers, including a series of genes associated with immune escape and drug resistance. In addition, we explored the roles of these genes in the mechanism of immune escape and drug resistance, and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCI. samples. Results: The major immune escape mechanisms of MCL included anti perforin activity, decreased immunogenicity and direct inhibition of apoptosis and cell killing, as mediated by type I and II B cells. The drug resistance mechanisms of different cell clusters included drug metabolism, DNA damage repair, apoptosis and survival promotion. Type III B cells closely communicate with other cells. The key genes involved in the resistance mechanisms showed dysregulated expression and may haw significant clinical prognostic value. Conclusion: This study investigated potential immune escape and drug resistance mechanisms in MCL. The results may guide individualized treatment and promote the development of therapeutic drugs.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 3 区 医学:研究与实验 3 区 肿瘤学
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出版当年[2018]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY
最新[2023]版:
Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [1]Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [2]Beijing Advaneed Inn ovati on Cen ter for Big Data-Based Precisi on Medicine, Beihang University and Capital Medical Un iversity, Beijing Tongren Hospital, Beijing 100730, China
通讯作者:
通讯机构: [1]Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China [2]Beijing Advaneed Inn ovati on Cen ter for Big Data-Based Precisi on Medicine, Beihang University and Capital Medical Un iversity, Beijing Tongren Hospital, Beijing 100730, China
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