Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Accumulation of abnormal B cells in spleen and lymph nodes is associated with resistance to treatment. A better understanding of the mechanisms controlling trafficking of leukemic cells to lymphoid organs is thus urgently needed. A research team from the Institute of Pharmacology and Structural Biology (IPBS - CNRS/Université Toulouse III - Paul Sabatier) has identified a molecule that plays a key role in the attachment of CLL cells to blood vessels in lymph nodes. These studies supported by ‘Laboratoire d’Excellence Toulouse Cancer’ (LABEX TOUCAN) and performed in close collaboration with ‘Institut Universitaire du Cancer de Toulouse (IUCT)’ and ‘Centre de Recherche en Cancérologie de Toulouse (CRCT)’, were published in BLOOD First Edition on July 10th 2015.
IPBS researchers used in vivo imaging in real time (intravital microscopy) to visualize the behavior of leukemic cells from human CLL patients within the lymph node microcirculation. They observed that leukemic cells, similar to lymphocytes, roll along the vessel wall, arrest for a few seconds and then roll again before stopping for a longer time.
IPBS team identified a molecule expressed at the surface of CLL cells (L-selectin) that plays a crucial role in their binding to the vessel wall. This molecule mediates the rolling of the leukemic cells and their arrest despite blood flow. An antibody that blocks the function of L-selectin inhibits the binding of CLL cells to lymph node blood vessels.Treated CLL cells can’t arrest in the blood vessels of the lymph node and leave the organ through the blood circulation. Interfering with migration of CLL cells to lymph nodes by blocking their interaction with blood vessels, represent a promising strategy to improve efficacy of cancer therapeutics currently used to treat CLL patients.
These findings have been obtained thanks to a fruitful collaboration between Jean-Philippe Girard’s team at IPBS, Jean-Jacques Fournié’s team at CRCT and Dr Loic Ysebaert from the hematology department at IUCT.
The work was funded by Laboratoire d’Excellence Toulouse Cancer (LABEX TOUCAN, Agence Nationale pour la Recherche), Fondation RITC, Région Midi-Pyrénées and Fondation ARC.
Visualization of leukemic cells from a CLL patient (green) in a lymph node blood vessel (red) This picture has been obtained using multiphoton microscopy in vivo. © Fanny Lafouresse and Jean-Philippe Girard, Institut de pharmacologie et de biologie structurale (CNRS/Université Toulouse III - Paul Sabatier)
L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo. Lafouresse F, Bellard E*, Laurent C*, Moussion C, Fournié JJ, Ysebaert L and Girard JP. BLOOD, 2015, in press
Researcher l Jean-Philippe Girard l T 05 61 17 59 18 / 59 67 l Jean-Philippe Girard