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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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Premalignant cell dynamics in indolent B-cell malignancies.
Pierre Milpied1, Bertrand Nadel, Sandrine Roulland
1aCentre d'Immunologie de Marseille Luminy, Aix-Marseille Université bINSERM U1104 cCNRS UMR7280, Marseille, France.
Current Opinion in Hematology
|June 8, 2015
Summary
Premalignant cells in follicular lymphoma and chronic lymphocytic leukemia (CLL) show distinct evolution dynamics. Understanding these early B-cell malignancies is key to preventing relapses.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) are indolent B-cell malignancies with long preclinical phases and frequent relapses.
- Premalignant cells play a crucial role in the development and progression of these diseases.
Purpose of the Study:
- To review recent findings on the occurrence, relevance, and dynamics of premalignant cells in FL and CLL.
- To propose distinct models of premalignant evolution for FL and CLL based on current research.
Main Methods:
- Review of recent scientific literature on premalignant cells in FL and CLL.
- Analysis of the role of B-cell receptor signaling, germinal centers, and lymph node microenvironment.
Main Results:
- Circulating cells with the FL hallmark translocation t(14;18) correlate with future FL risk.
- Chronic B-cell receptor stimulation drives clonal evolution and progression in FL.
- Lymph node microenvironment supports malignant cell proliferation in CLL and its precursor, monoclonal B-cell lymphocytosis (MBL).
Conclusions:
- FL premalignant cells (t(14;18) B cells) utilize memory B-cell dynamics to enter germinal centers, acquire mutations, and progress.
- CLL premalignant cells (CLL-like MBL) undergo germinal center-independent activation and proliferation within lymph nodes.
- Further genetic and functional analyses are needed to fully understand the origins and relapse mechanisms of FL and CLL.
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