Chronic Lymphocytic Leukemia: a light chain with heavy consequences
Chronic Lymphocytic Leukemia (CLL) cells, like other B lymphocytes, produce antibodies composed of 2 heavy chains and 2 light chains. Based on their sequence, these chains have been classified in hundred families and different sub-families. The Dr Basile Stamatopoulos of the Laboratory of Clinical Cell Therapy (LTCC) of Jules Bordet Institute (part of the ULB-Research Cancer Centers/U-CRC) in association with the University of Oxford and many other Belgian and European centers have just demonstrated that CLL patients carrying the IgLV3-21 light chain had a very aggressive disease and a decreased survival. Based on total RNAseq performed on 32 patients with an aggressive disease, the researchers discovered an abnormal frequency (28 %) of this light chain, four times higher than in an unselected population (7 %). In this small population, IgLV3-21 patients already presented a shorter treatment-free survival as well as a shorter overall survival. The poor prognosis of this light chain was thereafter confirmed on 3 independent cohorts for a total of more than 800 patients. These results highlight, for the first time, the potential role of the cell-autonomous signaling (independent from an external antigen) of these light chains which activates the leukemic cells leading to its resistance to spontaneous and chemotherapy-induced apoptosis. In the future, the presence of this IgLV3-21 light chain will allow to identify at diagnosis patients with a high risk of progression. These discoveries financed by “Télévie” and ”Les Amis de l’Institut Bordet” were published this week in Clinical Cancer Research journal.