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