Calorimetric Markers for Detection and Monitoring of Multiple Myeloma.

Abstract

Simple SummaryThis review highlights the potential of differential scanning calorimetry for multiple myeloma diagnosis and monitoring of the treatment outcome. The thermodynamic signatures of blood sera from patients with multiple myeloma are strongly dependent on the concentration and isotype of the secreted monoclonal immunoglobulins. Mathematical methods developed to analyze the biocalorimetry data and distinguish “diseased” from “healthy” thermogram to stratify plasma calorimetric profiles and determine specific interrelations between calorimetric and biochemical/clinical data are discussed.This review summarizes data obtained thus far on the application of differential scanning calorimetry (DSC) for the analysis of blood sera from patients diagnosed with multiple myeloma (MM) with the secretion of the most common isotypes of monoclonal proteins (M-proteins), free light chains (FLC) and non-secretory MM, as well as Waldenström macroglobulinemia and the premalignant state monoclonal gammopathy of undetermined significance. The heterogeneous nature of MM is reflected in the thermal stability profiles of the blood serum proteome of MM patients found to depend on both the level and the isotype of the secreted M-proteins or FLC. Common calorimetric markers feature the vast majority of the different myeloma types, i.e., stabilization of the major serum proteins and decrease in the albumin/globulin heat capacity ratio. A unique calorimetric fingerprint of FLC molecules forming amorphous aggregates is the low-temperature transition centered at 57 °C for a calorimetric set of FLC MM and at 46–47 °C for a single FLC MM case for which larger aggregates were formed. The calorimetric assay proved particularly advantageous for non-secretory MM and is thus a suitable tool for monitoring such patients during treatment courses. Thus, DSC provides a promising blood-based approach as a complementary tool for MM detection and monitoring.