Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS

Leukemia. 2013 Jan;27(1):208-12. doi: 10.1038/leu.2012.189. Epub 2012 Jul 11.


We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgGλ in IgGκ MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC-pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5-3.7; P<0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1-3.00; P=0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin Heavy Chains / blood*
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Isotypes / blood
  • Immunoglobulin Light Chains / blood*
  • Immunoglobulin Light Chains / chemistry
  • Immunophenotyping
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Monoclonal Gammopathy of Undetermined Significance / blood*
  • Monoclonal Gammopathy of Undetermined Significance / mortality
  • Monoclonal Gammopathy of Undetermined Significance / therapy
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Young Adult


  • Biomarkers
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes
  • Immunoglobulin Light Chains