Retrospective longitudinal monitoring of multiple myeloma patients by mass spectrometry using archived serum protein electrophoresis gels and de novo sequence analysis

M-proteins are antibody molecules produced by a clone of Multiple Myeloma cells. Thus, they are used as a disease activity marker. Traditionally, serum protein electrophoresis gels (SPEP) are used to quantify M-proteins. While effective for diagnostics, sensitivity of SPEP is limited. Here, we demonstrate that M-protein gels can be excised from SPEP gels, even when the band is undetectable by visible inspection. Clonotypic peptides are identified by de novo sequencing of mass spectrometry data, and these clonotypic peptides are then monitored in the longitudinal data covering the course of disease. Thus, it is possible to follow disease activity in a blood sample with a sensitivity that may be similar to that of minimal residual diseas platforms that rely on bone marrow biopsies.