Mantle cell lymphoma (MCL) is recognized as one of the most genetically heterogeneous diseases, with high instability at the genomic level. MCL is common in males with a male-to-female ratio of about 2:1, and its incidence accounts for 3%–10% of adult non-Hodgkin lymphoma cases. The evolutionary dynamics of MCL clones at the single-cell level remain largely unclear. Our research suggests that MCL may arise from multiple cells within the abnormal microenvironment of the entire hematopoietic lineage, particularly from initiating cells. These initiating cells predominantly consist of CD19−/IgM− subclones and exhibit a disrupted malignant clonal differentiation of pre-B cells along the tumor immunity evolution tree. Based on the single-cell transcriptome sequencing on the RedRock capture platform, we established the JeKo-1-LZ1 model, revealed the JeKo-1-LZ1 biology characteristics, and verified that the JeKo-1-LZ1 model was more representative than the JeKo-1-spheroid model by flow cytometry and sorting, colony forming experiment, and immunohistochemical and function analyses. Further details of our methodology can be found in the supplementary materials.