NEW YORKResearchers at the Joan and Sanford I. Weill Medical
College of Cornell University have identified a collection of
distinct chromosome translocations associated with monoclonal
gammopathy of undetermined significance (MGUS), a benign preclinical
phase of multiple myeloma.
It appears that there are at least four distinct molecular types of
multiple myeloma, each with a different translocation, Roy
Silverstein, MD, chief, Division of Hematology Oncology, said at a
The four different kinds of multiple myeloma look different
molecularly. They act differently in vitro, and they act differently
in patients, he said. So the disease we used to call
multiple myeloma has now been solved molecularly, and weve
discovered its not just one disease; its probably at
least four diseases.
P. Leif Bergsagel, MD, head of the team investigating the MGUS
mutations, said that the aim is to better understand the molecular
pathogenesis of multiple myeloma, a uniformly fatal plasma cell
neoplasm that accounts for 10,000 deaths a year in the United States.
Dr. Bergsagel, associate professor of medicine, and his colleagues
have identified three frequent chromosome translocation partners in
multiple myelomacyclin D1, fibroblast growth factor receptor 3
(FGFR3), and c-mafeach of which occurs in 20% to 25% of cases.
Several other infrequent translocations have been found as well.
These translocations occur at immunoglobulin heavy chain IgH switch
regions and activate critical oncogenes, setting off the chain of
events of tumorigenesis, Dr. Bergsagel said. He and his colleagues
are working to develop a model system to study the effects of
interfering with these critical events.
Such work will lead to rational drug design based on the molecular
biology of specific tumors, Dr. Silverstein said. We are close
to a major threshold in cancer therapeutics, he commented.