Yu Qiu: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China.
Xiao-Shuang Wang: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yuan Yao: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China.
Yan-Min Si: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xue-Zhu Wang: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China.
Ming-Nan Jia: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China.
Dao-Bin Zhou: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China.
Jia Yu: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xin-Xin Cao: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China. caoxinxin@126.com.
Jian Li: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Beijing, 100730, People's Republic of China. lijian@pumch.cn.
Waldenström's macroglobulinemia (WM) is an uncommon lymphoproliferative disorder, and the precise cellular landscape and the mechanisms of progression from IgM monoclonal gammopathy of undetermined significance (MGUS) to WM remain unclear. We performed single-cell RNA sequencing of CD19 + and CD19-CD38 + cells from healthy donors, IgM MGUS and WM patients. We found that samples from IgM MGUS and WM patients were composed of fewer early B-cell subsets and more T cells and NK cells than those from healthy controls. Compared with those of IgM MGUS patients, mature B cells of WM patients showed upregulation of HES1, GADD45B, NEAT1, DUSP22, RGS1, RGS16, and PIM1. We also identified a subpopulation of CD3 + CD19 + cells in IgM MGUS and WM patients, and trajectory analysis suggested that this subpopulation might be a stem cell-like subset. Further targeted gene sequencing of CD3 + CD19 + and CD3-CD19 + cells proved that MYD88 might be the early events in tumorigenesis according to variant allele fraction analysis. Additional subclonal hits such as CXCR4 and MAP2K1 mutations could be acquired during tumor progression. CXCL signaling, CCL signaling, IL2 signaling and TGFβ signaling pathways were involved in communication between CD3 + CD19 + cells and other immune cells. Our findings reveal the composition of CD38 + immune microenvironment together with B cells and plasma cells in IgM MGUS and WM patients, and provide comprehensive insights into mechanisms of progression from IgM MGUS to WM. The rare CD3 + CD19 + cells might be cells with "stemness" feature.
