Study sheds new light on two diseases affecting older populations
Splenic marginal zone lymphoma (SMZL) and chronic lymphocytic leukaemia (CLL) are two diseases that affect older populations (usually 70 years or older). Generally, both diseases progress slowly although most patients eventually require some form of treatment. Because the causes of both SMZL and CLL are yet to be fully understood, both diseases remain incurable. The EU-funded IGpath project hopes to change this. “We aim to shed new light on the development and progression of both CLL and SMZL, two comparable malignancies of mature B cells,” says Kostas Stamatopoulos, director, the Institute of Applied Biosciences at Greece’s Centre for Research and Technology Hellas (CERTH). The project was undertaken with the support of the Marie Skłodowska-Curie Actions. The research itself was conducted by Maria Gounari, a postdoctoral Marie Skłodowska-Curie fellow, and supervised by Stamatopoulos.
Two groundbreaking studies
In both CLL and SMZL, the malignant cells engage in complex interactions with the external world via specialised receptors. A critical player in these interactions is the B cell receptor immunoglobulin (BcR IG) – the focus of the IGpath project. Using innovative methodologies like next-generation sequencing, bioinformatics, molecular biology and biochemical assays, researchers explored the interaction of BcR IG with antigens in patients with CLL and SMZL. They also examined the functional and structural properties of such interactions. All laboratory findings were integrated with clinic-biological information, allowing the team to uncover new information that significantly broadens our understanding of how BcR IG contributes to the natural history of CLL and SMZL. “To date, IGpath is the largest functional and biochemical characterisation of BcR IG in CLL, offering solid links between the functional properties of the BcR IG and the clinical behaviour,” explains Gounari. “Furthermore, by analysing BcR IG from individuals with monoclonal B lymphocytosis (MBL), a pre-malignant condition, we shed light onto the BcR IG-antigen interaction processes prior to malignant transformation.” As to SMZL, the project completed the first systematic characterisation of the BcR IG in this disease, successfully highlighting distinctive features of BcR IG-antigen interactions. “Our results have the potential to assist in the refined stratification of patients based on the qualities of BcR IG interaction,” adds Stamatopoulos. “This, in turn, may lead to more precise, targeted therapies with obvious benefits to the patients and the healthcare system.”
Achieving new knowledge
IGpath has succeeded in revealing new information on the mode of interactions between BcR IG and antigen(s) in CLL and SMZL, thus highlighting the crucial links between IG structure/function and tumour behaviour. “The fruitful integration of different techniques, perspectives and expertise provided a comprehensive, holistic view of the involvement of BcR IG initiated processes in the pathogenesis of B cell malignancies,” concludes Stamatopoulos. Project researchers are now in the process of completing pending experiments and disseminating their findings.
Keywords
IGpath, diseases, splenic marginal zone lymphoma, SMZL, chronic lymphocytic leukaemia, CLL, monoclonal B lymphocytosis, B cells, B cell receptor immunoglobulin, BcR IG