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Single cell transcriptomic analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

By Haoyu Ruan, Zhe Wang, Yue Zhai, Ying Xu, Linyu Pi, Jihong Zheng, Yihang Zhou, Cong Zhang, RuoFan Huang, Kun Chen, Xiangyu Li, Weizhe Ma, Zhiyuan Wu, Jie Shen, Xuan Deng, Chao Zhang, Ming Guan

Posted 22 Apr 2020
medRxiv DOI: 10.1101/2020.04.18.20065805

Diffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

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