Aberrant plasma cells clonal composition in immunoglobulin light chain amyloidosis
Immunoglobulin light chain amyloidosis (AL amyloidosis) is a haematological disorder characterized by production of extra-cellular insoluble protein fibrils forming amyloid deposits that accumulate in various tissues and organs. AL amyloidosis develops, similarly as multiple myeloma (MM), from precancerous stage, monoclonal gammopathy of undetermined significance (MGUS). AL amyloidosis may coexist with other plasma cell dyscrasias, like MM. Genetic background determining MGUS to AL amyloidosis transition, as well as clonal architecture of combined AL amyloidosis and MM diseases has not been elucidated yet. We employ exome sequencing on FACS sorted population of aberrant plasma cells from all disease forms, MGUS, AL amyloidosis and combined AL amyloidosis and MM, to reveal i) the mutational profile typical for ALA and ii) to identify cancer drivers that distinguish precancerous MGUS from fatal ALA and iii) to trace the clonal evolution of AL amyloidosis combined with MM.
Genomic analysis of residual clone in multiple myeloma: approach for targeted therapy
Multiple myeloma (MM) is a plasma cell dyscrasia causing damage of multiple organs with fatal consequences for patients. Despite the success of modern therapies eliminating a vast bulk of the aberrant cells, surviving residual clones eventually lead to the relapse of the disease. Accumulation of genomic alterations during the stage of minimal residual disease (MRD) likely contributes to a selective grow advantage and survival under the drug pressure. Identification of specific mutations in MM patients with MRD can provide unique opportunities to target the residual plasma cell clones. We aim to identify mutations and deregulated gene expression in residual aberrant plasma cell population and to pinpoint molecular targets for precision medicine. To overcome the inevitable problem of very limited availability of study material, aberrant plasma cells, that complicates the large-scale mutation screening study, we use whole genome amplification technique followed by next-generation exome sequencing and customized bioinformatic pipeline.