Report: Analysis of beta-2 microglobulin (b2M), free HLA class I heavy chain (FHC) and the associated protein pattern in multiple myeloma (MM) patients from the Nordic Myeloma Group Study.

Background. Autologous stem cell transplantation is now considered the standard of care in young patients with multiple myeloma (MM) and the most consistent prognostic factor described at diagnosis has been blood levels of beta-2 microglobulin ((32m). Recently, the levels of (32mfree HLA class I heavy chain (FHC) has been shown to correlate with P2m but as expected not influenced by renal failure seen in MM. These data indicate that serum FHC may be a more useful disease marker than P2m in MM. The aim of this study was to evaluate the prognostic impact of FHC in a cohorde of 102 patients included in the NMSG study #5/94 and to identify B2m and/or FHC associated protein expression patterns identified by global array analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Methods. Serum samples from 102 patients with MM undergoing high dose therapy and autologous stem cell transplantation were retrospectively analyzed for concentration of B2m and FHC. The serum specimens were further evaluated by surface-enhanced laser desorption/ionization time-offlight mass spectrometry (SELDI-TOF-MS) to profile protein expression up to 20 kDa. Results. Serum 02m and FHC was correlated and B2rn but not FHC was found to be a most significant predictor ot overall survival. Using the SELDI technique with prefractiortation of samples before profiling, we identified mass spectrometry peaks significantly correlated to 132m and FHC and such circulating biomarkers with a likely pathophysiological role may be used as predictors of outcome. Conchtsiort. Data from this study did not confirm FHC as a prognostic variable indicating that the prognostic impact ot turn levels is not only a tumour marker but also an indirect consequence of other disease ielateci events including impaired kidney or other organ function as well as host-tumour interactions. The feasibility of a chip-based proteomic profiling technique to identify plasma proteins of prognostic significance will be demonstrated.