Related Experiment Video
Updated: Jun 24, 2026
Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma
Published on: March 30, 2018
Circulating B-cell chronic lymphocytic leukemia cells display impaired migration to lymph nodes and bone marrow
Tanja Nicole Hartmann1, Valentin Grabovsky, Wei Wang
1Laboratory for Immunological and Molecular Cancer Research, Third Medical Department, Salzburg University Hospital, Salzburg, Austria. t.hartmann@salk.at
Insights
Chronic lymphocytic leukemia (CLL) cells show reduced homing to lymph nodes and bone marrow due to impaired integrin function. Targeting lymphocyte function antigen-1 (LFA-1) may block CLL cell migration to survival niches.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Leukemic cell homing to secondary lymphoid organs and bone marrow is crucial for disease progression.
- Integrins, such as lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), play key roles in lymphocyte trafficking.
Purpose of the Study:
- To investigate the roles of LFA-1 and VLA-4 in the homing and transmigration of chronic lymphocytic leukemia (CLL) cells.
- To determine the impact of integrin expression and function on CLL cell localization in lymphoid organs.
Main Methods:
- Analysis of LFA-1 and VLA-4 expression on CLL cells.
- Assessment of CLL cell transmigration across endothelial cells expressing ICAM-1, VCAM-1, and CXCL12.
- In vivo homing studies using immunodeficient mice and tracking of normal B cells and CLL cells.
Main Results:
- CLL cells exhibited significantly reduced LFA-1 expression, linked to low beta2 integrin transcripts.
- VLA-4 expression was heterogeneous and activated by CXCL12, but CLL cells failed to transmigrate endothelium without sufficient LFA-1.
- Normal B cells homed to lymph nodes dependently on LFA-1, while CLL cells showed impaired homing to lymph nodes and bone marrow, but not the spleen.
Conclusions:
- CLL cells possess a diminished ability to adhere to and transmigrate through various endothelial barriers.
- CLL cells exhibit poor homing to lymphoid organs, except for the spleen.
- Integrin-blocking strategies could potentially prevent CLL cell migration to protective niches in lymph nodes and bone marrow.
Abstract:
Homing to secondary lymphoid organs and bone marrow (BM) is a central aspect of leukemic pathophysiology. We investigated the roles of the two major lymphocyte integrins LFA-1 and VLA-4 on B-cell chronic lymphocytic leukemia (CLL) cells in these processes. We found that the majority of CLL cells expressed significantly reduced LFA-1 due to low beta2 integrin transcripts. VLA-4 expression was heterogeneous but underwent rapid activation by the BM chemokine CXCL12. CLL cells failed to transmigrate across VCAM-1-expressing, ICAM-1-expressing, and CXCL12-expressing endothelium, whereas when LFA-1 expression was regained in subsets of CLL cells, these lymphocytes rapidly transmigrated the endothelium. Furthermore, when injected into tail veins of immunodeficient mice, normal B cells rapidly homed to lymph nodes (LN) in a LFA-1-dependent manner, whereas CLL cells did not. Nevertheless, only residual CLL subsets could reenter BM, whereas both normal and CLL cells homed to the mice spleen in an LFA-1-independent and VLA-4-independent manner. Our results suggest that CLL cells have a reduced capacity to adhere and transmigrate through multiple vascular endothelial beds and poorly home to lymphoid organs other than spleen. Integrin blocking could thus be an efficient strategy to prevent circulating CLL cells from reaching prosurvival niches in LNs and BM but not in spleen.
