Project: Research project

Project Details


The long-term objective of this Project is to determine the natural history
of monoclonal gammopathy of undetermined significance (MGUS). We will
determine the prevalence of MGUS in Olmsted County, Minnesota and then
follow asymptomatic prevalence cases as well as MGUS patients previously
recognized clinically in a prospective study. To ascertain long-term
outcome, we will also conduct a retrospective cohort study using clinically
recognized mGUS patients. Although the quality of medical information in
the Olmsted County population is excellent, the relatively small population
(106,000) poses some problems in obtaining enough cases for determining the
natural course of diseases of relatively low frequency. Therefore, we will
expand the study population to include cases from the remaining 10
Southeastern Minnesota counties. This is justified by the similarity of
MGUS patients in Olmsted County and Southeastern Minnesota on the basis of
their age, sex, race, size and type of M-protein found in our earlier
surveys. All cases of MGUS from the entire Southeastern Minnesota area
diagnosed from 1956 through 1994 will be followed in a retrospective cohort
study for survival and risk of multiple myeloma, macroglobulinemia, primary
amyloidosis, and other plasma cell proliferative disorders. We will follow
the survivors of the Southeastern Minnesota MGUS cohort that has been
followed retrospectively and new cases recognized after January 1, 1995
annually in a prospective study to determine the factors associated with
progression of MGUS to multiple myeloma and related disorders. This
project will also provide bone marrow and peripheral blood to Projects II
and III in order to investigate the molecular events in the transition of
MGUS to multiple myeloma. This includes determination of IL-6, IL-1, and
sIL-6R mRNA expression and serum levels of IL-6 and sIL-6R in patients with
MGUS and active multiple myeloma (Project II). The studies described in
Project III extend those of Project II by examining specific mechanisms
that may account for increased IL-6 production by the tumor itself such as
aberrant signaling and response to CD40 stimulation or deregulation of
pRb1. The potential to study patients with MGUS that progress to myeloma
from serial samples obtained through Project I will provide extremely
valuable information about the role of Il-6 in the progression of MGUS to
myeloma. Peripheral blood will be studied for the presence of circulating
myeloma cells in both MGUS and MM (Project IV). Hopefully, a better
understanding of the molecular events underlying the progression of MGUS
will result in the development of approaches to interfere with this
Effective start/end date9/30/941/31/11


  • Medicine(all)