机构:[1]Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China临床科室血液内科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[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首都医科大学附属北京同仁医院首都医科大学附属同仁医院[3]Nanning Life-Ontology Biotechnology Co., Ltd., Nanning 530000, China[4]Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China南方医科大学珠江医院
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.
基金:
National Natural Science Foundation of China (NSFC) [81873450]; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Tongren Hospital, Beihang University & Capital Medical University [BHTR-KFJJ-202009]
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
推荐引用方式(GB/T 7714):
Wang Liang,Mo Steven,Li Xin,et al.Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma[J].CANCER BIOLOGY & MEDICINE.2020,17(3):726-739.doi:10.20892/j.issn.2095-3941.2020.0073.
APA:
Wang, Liang,Mo, Steven,Li, Xin,He, Yingzhi&Yang, Jing.(2020).Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma.CANCER BIOLOGY & MEDICINE,17,(3)
MLA:
Wang, Liang,et al."Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma".CANCER BIOLOGY & MEDICINE 17..3(2020):726-739