Related Experiment Video
Updated: Jul 20, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma
Abstract:
Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.
Insights
Researchers identified a novel pre-plasmacytic cell in multiple myeloma and plasma cell leukemia. These cells, expressing common acute lymphoblastic leukemia antigen (CALLA), transform into plasma cells, offering insights into plasma cell malignancies.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Understanding plasma cell differentiation is crucial for diagnosing and treating plasma cell malignancies like multiple myeloma.
- Identifying distinct precursor populations can elucidate the pathogenesis of these hematological disorders.
Purpose of the Study:
- To investigate and characterize the cellular precursors of plasma cells in patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy.
- To identify specific cell surface markers that distinguish normal B-cell precursors from malignant plasma cell precursors.
Main Methods:
- Analysis of bone marrow samples from 28 patients using anti-B cell monoclonal antibodies (CD9, CD10, CD19-22, CD24).
- Flow cytometry to detect expression of common acute lymphoblastic leukemia antigen (CALLA, CD10) and terminal deoxynucleotidyl transferase (TdT).
- In vitro culture and stimulation of isolated CALLA+ cells with 12-0-tetradecanoyl-phorbol-13 acetate to assess differentiation potential.
Main Results:
- A population of lymphoid cells expressing CALLA (CD10) and HLA-DR, but lacking TdT, was identified in advanced multiple myeloma and plasma cell leukemia.
- These CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig) and B cell-associated antigens (CD9, CD19, CD22, CD24).
- CALLA+, Ig- cells were absent in benign monoclonal gammopathy and, upon in vitro stimulation, differentiated into plasma cells synthesizing myeloma-specific immunoglobulin chains.
Conclusions:
- The identified CALLA+, Ig- cells represent a pre-plasmacytic precursor population specific to plasma cell malignancies.
- These findings provide a cellular basis for understanding the development of multiple myeloma and plasma cell leukemia.
- Targeting this precursor population may offer novel therapeutic strategies for plasma cell neoplasms.
