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Multiple myeloma clones are derived from a cell late in B lymphoid development
J R Berenson1, R A Vescio, C H Hong
1Division of Hematology/Oncology, D.V.A. West Los Angeles, CA.
Current Topics in Microbiology and Immunology
|January 1, 1995
Summary
Multiple myeloma (MM) malignant cells originate late in B cell development. Researchers found no pre-class switch malignant cells, indicating MM likely arises from a mature B lymphocyte.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Multiple myeloma (MM) is a B cell malignancy characterized by a malignant clone with high somatic mutation.
- Immunoglobulin (Ig) heavy chain variable region (VH) sequences can identify MM malignant cells.
Purpose of the Study:
- To identify the specific B lymphocyte developmental stage from which the malignant clone in MM arises.
- To investigate the presence of CD10, CD34, and CD38 expressing cells within the MM tumor population.
- To determine the existence of pre-class switch malignant cells in MM patients.
Main Methods:
- Sequencing of VH regions from MM patients and generation of patient-specific complementarity determining region (CDR) primers.
- Polymerase chain reaction (PCR) amplification on purified cell subpopulations (CD10, CD34, CD38 positive/negative).
- PCR amplification with CDR and Cmu primers, followed by colony hybridization and sequencing to detect pre-class switch cells.
Main Results:
- A small fraction of CD10-expressing tumor cells was identified in MM patients.
- No CD34-expressing malignant cells were found in MM.
- While most tumor cells were CD38-positive, a small population of CD38-negative malignant cells was detected.
- No evidence of pre-class switch malignant cells was found, with very few colonies hybridizing to both Cmu and CDR3 probes.
Conclusions:
- The malignant clone in multiple myeloma likely originates from a cell late in B lymphocyte development.
- The absence of pre-class switch malignant cells suggests that the malignant transformation occurs after the B cell has undergone class switch recombination.