Scientific & Clinical
Bank on a cure® update
Myeloma Today in conversation with Dr. Brian Durie
What is the status of the initial phases of the
more rapid responses to thalidomide are associated
IMF's Bank On A Cure® project?
with higher risk of VTEs. It is important to note that
Bank On A Cure® is the world's first repository
VTEs were not associated with any of the blood
of DNA created to advance the understanding of
clotting genes, which supports the notion that
myeloma. The initial phases of this research proj-
aspirin can be helpful as a prophylactic treatment
ect, co-chaired by Drs. Gareth Morgan (Institute of
for VTEs.
Cancer Research, Royal Marsden Hospital, London)
These Bank On A Cure research findings were
and Brian Van Ness (Institute of Human Genetics,
presented at the annual meeting of the American
University of Minnesota, Minneapolis), have been
Society for Hematology (ASH) in December of 2006,
completed. We have developed a myeloma-specific
and a manuscript is now being finalized for publi-
single nucleotide polymorphism (SNP) chip. Once
cation, with Gareth Morgan as the senior author.
the custom chip was created, it took several months
An update will be presented at the International
to get the Affymetrix machines (which run the chip)
Myeloma Workshop (IMW) in June of 2007. This
set up and standardized, both in the US and in the
will be one of two Bank On A Cure oral presenta-
UK, and to get technicians familiarized with the
tions to take place at the IMW meeting in Greece.
process. Currently, the DNA samples collected from
several large clinical trials in the US and in Europe
What is the focus of the second research
are being analyzed.
Brian G.M. Durie, MD
project to be presented at the IMW meeting?
Aptium Oncology
Dr. Van Ness is working on a paper about the devel-
Can you briefly explain what SNPs are and how
Cedars-Sinai Comprehensive Cancer Center opment of our custom SNP chip evaluating the rela-
the custom chip works?
Los Angeles, California
tionships to survival and outcome. He is looking for
Single nucleotide polymorphisms (SNPs) are genetic
SNPs associated with event-free survival in patients
variations in DNA sequences, which can affect how we develop diseases
in two large clinical trials. Early analysis indicates that there may be detect-
and respond to pathogens, chemicals, drugs, etc. Our Affymetrix machines
able genetic differences between short- and long-term survivors, and that
are designed to process and analyze SNPs. While it is now possible to
it may be possible to predict which patients will need more aggressive
screen the human genome for half a million combinations of genes, such
therapies when they start their treatment. He is also comparing SNPs of
a process would be hugely cumbersome, so we have decided that it is
people who have myeloma with those who do not.
much more efficient to target a smaller group of SNPs that is more likely
to be relevant in myeloma. To proceed with a more focused and targeted
Can you tell us about the Bank On A Cure research projects you
approach, the Bank On A Cure research team helped select the 3,404
recently completed?
SNPs associated with gene functions that we think are most relevant to
I looked at the impact of genetic variation on bone disease, focusing on
the regulation of myeloma growth, disease progression, response to treat-
SNPs that correlate with the likelihood that a myeloma patient would get
ment, drug metabolism, bone microenvironment, immune responses,
bone disease. We analyzed genes related to various end points within the
DNA repair, and predisposition to side effects like neuropathy, mucositis,
data set from the 256 myeloma patients who were enrolled in Total Therapy
or deep vein thrombosis (DVT). Our custom chip includes all the major
II (TT II), a clinical trial by Drs. Bart Barlogie and John Shaughnessy at
sequences where a change in the gene can relate to myeloma.
the Myeloma Institute for Research and Therapy in Little Rock, AR. When
it comes to accurately documenting the presence or absence of bone
Can you give us an example of a discovery made from the data
disease, the TT II data set is the strongest anywhere in the world because
processed so far?
all 256 patients got whole body x-ray and MRI plus PET imaging studies
One of the Bank On A Cure projects sought to identify genetic pathways
performed as necessary. In this Bank On A Cure study, we found that
that may explain why an estimated 15% to 30% of myeloma patients
there are several SNPs related to bone disease, four of them linked to the
treated with thalidomide suffer venous thromboembolisms (VTEs), or
production of a peptide that enhances the formation of osteoclasts, MIP1-
blood clots, as a major complication. We looked at data on 394 myeloma
alpha. The SNP data analysis is now complete, and we have developed a
patients produced from three clinical trials, two performed in Europe and
prognostic tool to help evaluate whether a myeloma patient is likely to get
one in the US. We identified four gene clusters associated with the VTEs. It
bone disease. A paper on the subject is being prepared.
was discovered that the risk of developing VTEs while on thalidomide was
mostly related to the genes that control inflammation, with IL6 and TNF
What's next for Bank On A Cure?
shown to be the main cytokines to influence inflammation within blood
There are many exciting research projects emanating from the Bank On
vessels. Other genes related to drug processing and metabolism have
A Cure DNA repository. Readers of Myeloma Today should stay tuned for
also been linked to the risk of VTEs, which might relate to how quickly
further developments, which will also be disseminated through the IMF's
a patient responds to treatment. If a patient has a dramatic response to
weekly email updates, Myeloma Minute, as well as the IMF website website
thalidomide, the rapid release of all of the products from the breakdown
www.myeloma.org. mt
of the dying myeloma cells can promote clotting via inflammation. So, the

www.myeloma.org

---