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Differential expression of CD56 and CD44 in the evolution of extramedullary myeloma
Inger Marie S Dahl1, Thomas Rasmussen, Goran Kauric
1Section of Haematology, University Hospital, Tromsø, Norway. medimd@rito.no
Abstract:
We report on the different expression of CD56 and CD44 in plasma cells (PCs) simultaneously collected from bone marrow, extramedullary locations and peripheral blood in seven patients with multiple myeloma. Extramedullary PCs showed absence of CD56. In the bone marrow, however, subsets with varying CD56 expression were found in five out of seven patients, with one subset corresponding to that of extramedullar PCs. This differs from the de novo downregulation of CD56 in PC leukaemia, and suggests different mechanisms of spread of myeloma cells. CD44 expression was generally upregulated on extramedullary PCs. In three of the patients we investigated the clonal origin of extramedullary myeloma cells by sequencing the variable portion of the heavy chain immunoglobulin gene in phenotypically defined PCs isolated from different locations. In each patient we found malignant PCs with different homing behaviour originating from a common precursor cell.
Insights
Multiple myeloma plasma cells (PCs) show varied CD56 expression in bone marrow but lack it in extramedullary sites. This suggests distinct myeloma cell spread mechanisms and clonal origins.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Multiple myeloma is characterized by malignant plasma cells (PCs).
- Understanding the behavior and markers of myeloma PCs in different body locations is crucial for treatment.
- CD56 and CD44 are cell surface markers investigated for their role in myeloma progression.
Purpose of the Study:
- To investigate the differential expression of CD56 and CD44 in multiple myeloma PCs from various anatomical sites.
- To explore the clonal origin and homing behavior of extramedullary myeloma cells.
Main Methods:
- Simultaneous collection of plasma cells from bone marrow, extramedullary locations, and peripheral blood.
- Immunophenotyping for CD56 and CD44 expression.
- Sequencing of the variable heavy chain immunoglobulin gene to determine clonal origin.
Main Results:
- Extramedullary PCs consistently lacked CD56 expression.
- Bone marrow PCs exhibited variable CD56 expression, with some subsets mirroring extramedullary PCs.
- CD44 was generally upregulated on extramedullary PCs.
- Clonal analysis confirmed that extramedullary myeloma cells originated from a common precursor cell.
Conclusions:
- Differential expression of CD56 and CD44 in myeloma PCs suggests distinct mechanisms of dissemination and homing.
- Myeloma cells can spread to extramedullary sites while altering their surface marker expression.
- Extramedullary myeloma is often derived from a common clonal precursor, indicating complex cellular dynamics.