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Updated: May 13, 2026
A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations
Published on: October 25, 2018
Intraclonal heterogeneity in concomitant monoclonal lymphocyte and plasma cell populations: combining flow cytometric
Barbara K Zehentner1, Monica E de Baca, Denise A Wells
1HematoLogics, Inc, Seattle, WA, USA. barbara@hematologics.com
Insights
Flow cytometry and gene rearrangement analysis identify distinct B-cell and plasma cell populations in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (LPL). This helps determine if clonal processes are related, guiding patient monitoring and outcome prediction.
Area of Science:
- Hematology
- Molecular Biology
- Immunology
Background:
- Flow cytometric cell sorting and gene rearrangement analysis are crucial for characterizing distinct B-lymphoid and plasma cell populations.
- Previous work established monoclonality profiles for lymphoplasmacytic lymphoma (LPL) bone marrow aspirates, suggesting unrelated genetic processes are more common.
Observation:
- This study demonstrates the combined utility of cell sorting with gene rearrangement (IgH, IgK), IgVH sequencing, and FISH analysis in clinical Waldenström macroglobulinemia/LPL cases.
- Multiple distinct B-cell and plasma cell populations were identified in patients with suspected Waldenström macroglobulinemia/LPL.
Findings:
- Combining cell sorting with molecular analysis proves the presence of identical monoclonal genotypes for Waldenström macroglobulinemia/LPL.
- Distinct lymphoid and plasma cell populations can have non-identical genotypes, indicating multiple clonal processes.
Implications:
- Understanding the number of clonal processes (molecular profiles) present is vital for guiding patient monitoring during treatment.
- Identifying distinct clonal processes may help predict patient outcomes and potentially identify those with worse prognoses.
Abstract:
Flow cytometric cell sorting combined with molecular gene rearrangement analysis can assist in further characterizing simultaneously occurring, phenotypically distinct, monoclonal B-lymphoid and monoclonal plasma cell populations that express immunoglobulin of the same light chain. We previously established monoclonality profiles for lymphoid and plasma cell populations of lymphoplasmacytic lymphoma (LPL) bone marrow aspirates by using flow cytometric cell sorting and subsequent monoclonal gene rearrangement analysis. Our findings demonstrated that related genetic processes are less likely than unrelated genetic processes. Here, we demonstrated the utility of cell sorting combined with gene rearrangement (both immunoglobulin IgH and IgK) and IgVH sequence analysis as well as plasma cell targeted fluorescence in situ hybridization analysis in clinical cases of presumed Waldenström macroglobulinemia/LPL in which multiple distinct B-cell and plasma cell populations were identified. Combining cell sorting with subsequent molecular analysis can provide proof of identical monoclonal genotype for Waldenström macroglobulinemia/LPL and nonidentical distinct lymphoid and plasma cell populations in the clinical setting. Understanding how many clonal processes (molecular profiles) are present can help guide patient monitoring throughout treatment and potentially identify patients with worse outcomes.
