Could Clonotypic B Cells Be the Key to Myeloma & AL Amyloidosis Origins? | Bruno Paiva, PhD | EHA25

I'm Bruno Paiva from the University of Navarre in Pamplona, Spain. At EHA 2025 we are presenting an oral abstract trying to uncover what is the phenotype of the cell of origin of myeloma as well as light chain amyloidosis. This is a very complex and hardworking study, but to keep the long story short, I would highlight that indeed we find immature cells all the way to the B-cell precursor that may share the same monoclonal immunoglobulin gene rearrangement we see in tumour plasma cells, both from myeloma and light chain amyloidosis. We see also mature B-cells carrying this clonal VDJ receptors. These cells have the same phenotypic traits as to normal cells of that differentiation stage so these are bona fide immature cells and not myeloma cells that are de-differentiated. Importantly, these cells not only share the same immunoglobulin, they also share a lot of somatic mutations with tumour cells, but these somatic mutations are mainly random. They do not affect genes that are a driver in these two plasma cell neoplasms and we also do not see typical copy number variations that you typically find in a patient with myeloma or light chain amyloidosis. And therefore we believe that these cells were there in the origin of these diseases, but are not drivers of relapse and we believe this is a very important finding because in to some extent the presence of these cells may lead into some false positive results when we are monitoring treatment efficacy based on sequencing versus immunophenotypic methods. And in fact we show data suggesting that this hypothesis is true both in myeloma as well as light chain amyloidosis. The abstract is being presented on Friday afternoon by one of our PhD students Carmen Gonzalez.