IgH Translocation as Seminal Events in MGUS and Myeloma

  • Therneau, Terry M (PI)
  • Jelinek, Diane F (PI)
  • O'Fallon, W. (PI)
  • O'Fallon, W. Michael (PI)
  • O'Fallon, W. (PI)
  • Last, John (PI)
  • O'Fallon, W. Michael (PI)
  • van Ness, Brian (PI)
  • Kyle, Robert (PI)
  • Fonsecar, Rafael (PI)
  • Greipp, Philip (PI)
  • Lust, John Anthony (PI)
  • Michael O'Fallon, W. (PI)

Project: Research project

Project Details


This is a multifaceted Program consisting of four Projects designed to
increase our understanding of the cellular and molecular feature of the
monoclonal gammopathy in order to develop more effective therapy. The
Program Project will expand our limited experience with long-term follow-up
of patients with monoclonal gammopathy of undetermined significance (MGUS).
Based upon our past experience, one-fourth of patients with an apparently
benign monoclonal gammopathy will develop serious disease such as multiple
myeloma, macroglobulinemia, amyloidosis, or related disorders over long-
term follow-up. Two Cores are included: Core will centralize the
collection of peripheral blood, serum and bone marrow from patients with
monoclonal gammopathies, and Core 9007 will be responsible for all
epidemiological, statistical, and data management aspects of the Program
Project. Dr. Kyle, in Project I, will determine the prevalence of MGUS in
Olmsted County. He will conduct a retrospective study of survival and risk
of multiple myeloma, primary amyloidosis, and other plasma cell
proliferative disorders that have been recognized in Southeastern Minnesota
(including Olmsted County) from 1960 through 1994. In addition, he will
follow all survivors of the Southeastern Minnesota MGUS cohort and all
subsequently newly diagnosed cases in a prospective study to ascertain
their outcomes. Bone marrow cells and serum will be collected through the
Core A facility which will be critical for much of the subsequent research
projects. Dr. Lust, in Project 2, will ascertain the role of IL-1beta and
IL-6 in the progression of MGUS to multiple myeloma. He has demonstrated
the existence of a novel IL-6 receptor (IL-6R) mRNA in myeloma cells that
encodes a soluble form of the IL-6R. We propose to develop a soluble IL-6R
that will inhibit IL-6 activity. In Project 3, Dr. Jelinek will ascertain
the role of CD40 expression in myeloma cells and determine expression
patterns of the natural ligand for CD40 in MGUS and myeloma patients. She
will also determine the role of the product of the retinoblastoma gene
(pRb1) in CD40 signalling and production of IL-6 and will characterize the
expression of pRb1 in MGUS and myeloma patients. Drs. Van Ness and Witzig,
in Project 4, will identify, quantitate, and characterize circulating
plasma cells and clonally related cells in patients with MGUS and multiple
myeloma using immunofluorescence microscopy, flow cytometry, and tumor-
specific ASO-PCR techniques. They will also examine the ability of sorted
populations of cells from myeloma patients to differentiate and expand in
cytokine supplemented cultures in SCID mice. We anticipate that the
studies proposed in this Program Project will clarify the molecular and
cellular changes that occur in patients with benign monoclonal gammopathy
prior to the development of multiple myeloma or related disorders. We hope
this will lead to novel therapeutic strategies.
Effective start/end date9/30/941/31/11


  • Medicine(all)