Clin Cancer Res. 2011 Apr 1;17(7):1692-700. Epub
2011 Feb 16.
The progression from MGUS to
smoldering myeloma and eventually to multiple
myeloma involves a clonal expansion of genetically
abnormal plasma cells.
López-Corral L, Gutiérrez NC, Vidriales MB,
Mateos MV, Rasillo A, García-Sanz R, Paiva B,
San Miguel JF.
Servicio de Hematología, Hospital Universitario,
Universidad de Salamanca, Salamanca, Spain.
Abstract
PURPOSE:
Genetic aberrations detected in multiple
myeloma (MM) have also been reported in the
premalignant conditions monoclonal gammopathy of
undetermined significance (MGUS) and smoldering
MM (SMM). Our aim was to investigate in depth
the level of clonal heterogeneity of recurrent
genetic abnormalities in these conditions.
EXPERIMENTAL DESIGN:
Immunoglobulin heavy chain (IGH)
translocations, 13q14 and 17p13 deletions, and
1q21 gains using FISH were evaluated in 90 MGUS,
102 high-risk SMM, and 373 MM. To this end, we
not only purified plasma cells (PC) for the FISH
analysis (purity > 90%), but subsequently, we
examined the correlation between the proportion
of PC with cytogenetic changes and the number of
clonal PC present in the same sample, as
measured by multiparametric flow cytometry.
RESULTS:
We observed a significant difference between
the proportion of clonal PC with specific
genetic abnormalities in MGUS compared with SMM
and in SMM compared with MM. Thus, the median
proportion of PC with IGH translocations
globally considered, t(11;14) and 13q deletions
was significantly lower in MGUS than in SMM, and
in SMM than in MM [IGH translocations: 34% vs.
57% vs. 76%; t(11;14): 38% vs. 61% vs. 81%; and
13q deletion: 37% vs. 61% vs. 74% in MGUS, SMM,
and MM, respectively]. For t(4;14), the
difference was significant in the comparison
between MGUS/SMM and MM and for 1q between MGUS
and SMM/MM.
CONCLUSIONS:
This study demonstrates that the progression
from MGUS to SMM, and eventually to MM, involves
a clonal expansion of genetically abnormal PC.
- PMID: 21325290 [PubMed - in process]