[parkerpeter]

New study - progression of MGUS and smoldering myeloma

by parkerpeter on Thu Feb 17, 2011 6:12 am

Interesting new study. Heard about a study that will be proceeded at Washington University, St. Louis:

Lopez-Corral, et al., "The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells", Clinical Cancer Research, 2011 Apr 1;17(7):1692-700.

Abstract:

Purpose:Genetic aberrations detected in multiple myeloma (multiple myeloma) have also been reported in the premalignant conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (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 fluorescence in situ hybridization (FISH) were evaluated in 90 MGUS, 102 high-risk SMM and 373 multiple myeloma. 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 multiple myeloma. 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 multiple myeloma (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 multiple myeloma, respectively). For t(4;14) the difference was significant in the comparison between MGUS/SMM and multiple myeloma and for 1q between MGUS and SMM/multiple myeloma.

Conclusions:This study demonstrates that the progression from MGUS to SMM, and eventually to multiple myeloma, involves a clonal expansion of genetically abnormal PC.

http://clincancerres.aacrjournals.org/content/early/2011/02/16/1078-0432.CCR-10-1066.full.pdf