This study systematically evaluates the dynamic changes in circulating non-malignant B cells (NMBCs) in chronic lymphocytic leukemia (CLL) patients post-treatment and their significant association with hematological recovery, polyclonal antibody production, and prolonged progression-free survival. Utilizing high-dimensional mass cytometry (CyTOF) combined with multiple algorithms, the research reveals NMBCs as independent prognostic factors and provides supplementary information for minimal residual disease (MRD) assessment.
Literature Overview
This article, 'Re-emergence of circulating non-malignant B cells as a prognostic biomarker in chronic lymphocytic leukaemia', published in Scientific Reports, reviews the dynamic changes in non-malignant B cells (NMBCs) and their clinical significance in CLL patients following chemoimmunotherapy (CIT). By analyzing 201 blood samples using high-dimensional mass cytometry (CyTOF), the study demonstrates that NMBC recovery correlates with hematological function and polyclonal antibody production, with early recovery showing significant association with prolonged progression-free survival.
Background Knowledge
Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterized by clonal proliferation of CD5+ B cells, frequently accompanied by disruption of the immune microenvironment and suppression of normal B-cell function. As CLL cells accumulate in blood, bone marrow, and secondary lymphoid organs, traditional minimal residual disease (MRD) assessment has primarily relied on bone marrow testing. However, NMBC recovery in peripheral blood may reflect CLL cell clearance in secondary lymphoid organs. While molecular markers of CLL (e.g., CD5, CD20, CD79b, CD43, ROR1) have been extensively studied, the clinical implications of NMBC recovery post-treatment remain underexplored. Recent advances in high-dimensional single-cell technologies have created new opportunities for distinguishing malignant and non-malignant cells, enabling systematic analysis of NMBC dynamics in relation to treatment response and prognosis.
Research Methods and Experiments
The study enrolled 79 previously untreated CLL patients, collecting 201 blood samples for analysis using a 24-antibody mass cytometry (CyTOF) panel. FlowSOM and UMAP algorithms identified CD19+ B-cell clusters with non-malignant phenotypes (NMP), including one memory-type (CD27+CD38−) and two naïve-type (CD27−CD38+) NMBC subsets. Independent validation of NMBCs was performed using flow-cytometry gating strategies based on non-redundant markers (CD5−CD43−ROR1−CD20hiCD79bhiCD81+), with correlations to MRD status, hematological recovery, and immunoglobulin levels evaluated.
Key Conclusions and Perspectives
Research Significance and Prospects
This study systematically demonstrates the relationship between circulating NMBC recovery and long-term prognosis in CLL patients post-treatment, establishing their potential as complementary biomarkers to MRD for assessing CLL cell clearance in secondary lymphoid organs. Future research should validate the prognostic value of NMBCs in alternative treatment regimens (e.g., BTK inhibitors) and explore their application in guiding personalized treatment durations.
Conclusion
Through high-dimensional mass cytometry analysis, this study systematically characterized the dynamic changes in non-malignant B cells (NMBCs) among chronic lymphocytic leukemia (CLL) patients receiving chemoimmunotherapy (CIT). The research identifies early post-treatment NMBC cluster size as an independent prognostic factor for progression-free survival (PFS), demonstrating its correlation with hematological function and polyclonal antibody production. Notably, NMBC recovery provides additional prognostic information even in patients with persistent MRD positivity, particularly when NMP clusters exceed 2.68%. These findings offer novel perspectives for treatment monitoring and prognosis evaluation in CLL, establishing a foundation for clinical strategies integrating both MRD and NMBC assessments.
