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Chronic lymphocytic leukemia with prostate infiltration mediated by specific clonal membrane-bound IgM
Carol A Bogdan1, Alice A Alexander, Miroslaw K Gorny
1Medical Service, New York Harbor Healthcare System, New York 10010, USA.
Insights
Chronic lymphocytic leukemia (CLL) can rarely infiltrate atypical sites like the prostate. This study reveals that specific surface-bound IgM on CLL cells mediates prostate infiltration by binding to prostate cell antigens.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Chronic lymphocytic leukemia (CLL) typically involves hematopoietic organs.
- Atypical infiltration of CLL cells into single sites is rare and poorly understood.
- The specific mechanisms driving unusual CLL cell distribution remain uninvestigated.
Purpose of the Study:
- To investigate the mechanism behind atypical prostate infiltration in chronic lymphocytic leukemia.
- To determine if specific molecular interactions mediate CLL cell binding to prostate tissues.
Main Methods:
- Collected peripheral blood from early-stage CLL patients with prostate infiltration.
- Performed in vitro binding assays of CLL cells to prostate and other cell lines.
- Created hybridomas from CLL cells to generate monoclonal antibodies.
- Utilized flow cytometry and immunohistochemistry to analyze IgM binding.
Main Results:
- CLL cells from patients with prostate infiltration exhibited strong in vitro binding to prostate cell lines.
- CLL cells from patients without prostate infiltration did not bind to prostate cells.
- Monoclonal IgM from hybridomas specifically bound to prostate cells and blocked CLL cell adhesion.
- Flow cytometry and immunohistochemistry confirmed specific IgM binding to prostate cells.
Conclusions:
- Specific surface-bound IgM on CLL cells, targeting prostate-specific antigens, mediates atypical prostate infiltration.
- This mechanism may also explain CLL infiltration into other atypical organs.
- Understanding this interaction opens avenues for targeted therapies in CLL.
Abstract:
Chronic lymphocytic leukemia (CLL) is characterized by an accumulation of monoclonal B lymphocytes in the hematopoietic organs. Rarely, CLL cells accumulate in a single atypical site. The mechanism underlying this unusual distribution of CLL cells has not been studied previously. We obtained peripheral blood from five patients having early stage CLL with heavy prostate infiltration. These patients' circulating CLL cells bound strongly in vitro to cultured prostate cell lines PC3, LNCaP, and DU145 and to short-term cultures of fresh prostate cells but not to colon, breast, or bladder cells. CLL cells from patients without prostate infiltration did not bind in vitro to any cell line. Peripheral blood CLL cells from one patient with CLL with heavy prostate infiltration were fused with a mouse-human heteromyeloma line to make hybridomas expressing the same monoclonal IgM as the patient's CLL cells. The hybridoma cells bound specifically to prostate cells. IgM secreted by the hybridoma blocked binding of the patient's CLL cells to prostate cells. Flow cytometry and immunohistochemistry demonstrated that the secreted IgM bound specifically to prostate cells. These results indicate that CLL with atypical prostate infiltration can be mediated by specific surface-bound IgM against an antigen expressed specifically by prostate cells and suggest that a similar mechanism might also apply to cases of CLL with atypical infiltration into other organs.
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