A PUBLICATION OF
UAMS MYELOMA INSTITUTE
FALL 2016
PERSONALIZED MEDICINE THROUGH COMPUTATIONAL BIOLOGY
Dear Readers,
“It is the partnership between our sophisticated research and clinical components that gives us an edge in making a cure a reality.”
I am pleased to share with you my excitement about discoveries in myeloma biology that are unfolding at a rapid rate and raising the bar for effective, precision treatment. As you will learn in this issue of Myeloma, a collaborative international study has revealed gene variants that increase the risk of developing myeloma. These findings have given us new insights into the biological mechanisms of myeloma development and are helping us craft strategies for myeloma prevention. Additionally, our talented research team is mining and integrating large data sets in order to zero in on the subtleties involved in molecular relationships and processes that support myeloma growth. While our laboratories are busy with novel scientific investigation and our bioinformatics experts are analyzing “big data,” our clinicians are focused on delivering comprehensive patient care with compassion, expertise and overall excellence. It is the partnership between our sophisticated research and clinical components that gives us an edge in making a cure a reality. We look to our supporters to help us maintain the momentum of our cutting-edge research and clinical care. The generosity of so many donors who believe in our program makes it possible for us to advance curative treatments and bring promise to patients worldwide. In the spirit of the holiday season, I hope you will respond to our annual appeal in this issue of Myeloma and help us make the future brighter for patients and their families. My thanks and gratitude in advance. Cheers and kind regards,
Gareth Morgan, M.D., Ph.D. Director, UAMS Myeloma Institute 2
myeloma.uams
edu
Big Data Analysis . . . . . . . . . . . . . . . . . . . 4 20 Years & Going Strong . . . . . . . . . . . . . . . . 8
FALL 2016
Crystals4Cancer . . . . . . . . . . . . . . . . . .
EDITOR Janet Aronson CREATIVE DIRECTOR Laurie Shell
Publication . . . . . . . . . . . . . . . . . . . . . . 11
GRAPHIC DESIGNER Eight New Mindy Individuals Stout with disease PHOTOGRAPHER Johnpaul Jones
Individuals without disease
GeneCh
ip
DIRECTOR UAMS Myeloma Institute Gareth Morgan, M.D., Ph.D. sis ATH
Genetic Risk Factors . . . . . . . . . . . . 14
An Active Outdoor Life Dispite Myeloma
GeneCh
Arabidop
1 Genome
CHANCELLOR University of Arkansas for Medical Sciences Dan Rahn, M.D.
Phone: (501) 526-2873 myeloma.uams.edu
SNP 2
Arabidop
ip
sis ATH
1 Genome
'All in' for Clinical Care Excellence
Using a CHIP can gen . . . . . . . 21 otype . 5000,000 -5 Million SNPs
. . . . . . . . . . . 22
SNP 1 No association to disease
4
The development of personalized medicine approaches to treating myeloma and related diseases takes center stage in this issue of Myeloma. With a wealth of patient samplederived data, sophisticated systems for analyzing the data, and talented experts who can interpret the analyzed data, the Myeloma SNP 3Institute is making significant progress in the understanding of myeloma biology at the molecular level. This enables our translational research team to get better answers to questions related to diagnosis and treatment and maximize the potential for improved health. myeloma.uams
edu
. . . . . . . . 18
"Now you all find a cure for this disease"
SNP 1
Myeloma is published twice a year by the Myeloma Institute, University of Arkansas for Medical Sciences 4301 W. Markham St. #816 Little Rock, AR 72205
10
14
22 SNP 2
Making a difference in the lives of patients Nothe association and their loved ones is what makes Myeloma Institute tick. It is the basisto of disease our focus and drive, and it is exemplified by our patients’ stories. We hope all patients have access to care that is informed by advances in personalized medicine approaches and that offers a new lease on life. We welcome your comments. Feel free to contact us via email. Sincerely, Janet Aronson Editor
SNP 3 Associated to disease
AronsonJanetL@uams.edu
3
The bioinformatics team: (left to right) Chris Wardell, team leader, Michael Bauer, Amy Buros, Cody Ashby and Caleb Stein
Big Data Analysis Fuels Personalized Medicine “We can sequence a
to treatment. Data from current
Myeloma Institute is its wealth
patients is continually added to the
of patient-derived clinical and
collection. Additionally, the Myeloma
research data. With more than 11,750
Institute’s large tissue specimen
patients over a period of 27 years,
archive presents the opportunity to
the Myeloma Institute has amassed a
mine even more data, utilizing today’s
treatment to
treasure trove of data elements, many
sophisticated analytics tools.
the mutation
at the molecular level, that have the
person and their cancer and then target
that is out of kilter.” 4
A
truly unique feature of the
A single patient can generate a lot
potential to yield new understandings
of meaningful pieces of data — up
of disease biology and response
to 100,000 — based on information myeloma.uams
edu
gleaned from the 20,000 to 30,000
retrieval, use and sharing of biomedical data.
genes in the human genome.
It encompasses the utilization of existing
Data are derived from patient
computational and statistical methods and
samples that are subjected to
algorithms, as well as the development of
DNA sequencing, gene expression
new methods to extract knowledge from
profiling, and proteomics expression
the underlying data and advanced decision
studies and are annotated with
support systems to improve clinical practice.
various patient information such as
BMI is integral across the whole spectrum
age, sex and disease state.
from molecules to populations, bridging basic
Multiplying so much data by thousands of patients results in
and clinical research and practice. At the Myeloma Institute, we are striving to
“Big Data.� Big Data implies large
better understand the intricate network of
volume and complexity, such that
molecular processes involved in myeloma. The
advanced mathematics and large,
vast amounts of molecular and clinical data
high-performance computers are
that we have amassed via genome sequencing
needed. Big Data requires very
and other high-throughput techniques
big computers, massive amounts
(large-scale methods to purify, identify and
of storage, and sophisticated
characterize DNA, RNA, proteins and other
mathematics.
molecules) contain crucial information with the
Computational biology, also known
potential of leading to development of more
as bioinformatics, is the field of
effective, targeted therapies. We are mining
using computer-based analysis and
and integrating these data, and resolving
statistics to understand biology.
the subtleties involved in the pathways and
It covers both basic research (in
molecular relationships that support myeloma
the laboratory) and translational research
growth. By identifying molecular patterns
(developing clinical applications from basic
that characterize each individual genome
research), and spans the full spectrum from
and discerning which of these individual
molecules to human population studies.
variations is related to a disease subset or
Computational biology/bioinformatics is a
response to treatment, we can further the
subset of Biomedical Informatics (BMI).
development of tools for diagnosis, prognosis
BMI is focused on the management of large data sets in health care. It is a means
and personalized treatment. We do this, in part, through the identification
of organizing and understanding data and
of disease-related SNPs (single nucleotide
turning it into knowledge, with the overarching
polymorphisms) derived from large-scale
goal of improving human health, and is
techniques. Mutations in the genomic
an integral part of the search for disease-
code often produce changes in the protein
associated genes. An interdisciplinary
sequence, leading to diseases. The key to
field, BMI involves the development, study
approaches that identify disease mutations
and application of theories, methods and
lies in distinguishing between SNPs that are
processes for the generation, storage,
functionally relevant from those that are not.
myeloma.uams
edu
5
SNP is a DNA sequence variation occurring when a single nucleotide adenine (A), thymine (T), cytosine
1
(C) or guanine (G) in
SNP
the genome (or other
2
shared sequence) differs between members of a species or paired chromosomes in an individual. (Source: https://ghr.nlm.nih.gov/ primer/genomicresearch/snp)
=A
=T
=C
=G
Christopher Wardell, Ph.D., an experienced bioinformatician with particular expertise in next-generation sequencing, joined the Myeloma
resolution technology is essential. In terms of sample quantity, the Myeloma
Institute in July. Educated and trained in the
Institute is unsurpassed. “We have one of the
UK, Wardell was a lead bioinformatician at The
largest repositories of myeloma specimen
Institute of Cancer Research in the UK and
samples in the world. Using today’s modern
a research scientist with the Laboratory for
tools, we can take current data, compare it with
Genome Sequencing Analysis at the RIKEN
data in the repository, and use this information to
Center for Integrative Medical Sciences in Japan.
direct future research and treatment strategies.
“We are aiming to spot the differences — to see what makes a normal cell become cancerous,” Wardell said. “By comparing the normal genome
This puts us in a distinctive position,” Wardell said. Having so much data enables drill-down to
of a patient to the genome of their tumor, we
a very detailed level of information. Given the
can identify the DNA changes that predispose
volume of data, the process is time consuming.
and cause someone to develop cancer.”
“But, processes that have been slow in the
The ultimate goal is personalized medicine.
past are speeding up. Computational speed and
“We can sequence a person and their cancer
capacity doubles every 18 months,” Wardell said.
and then target treatment to the mutation or
Recognizing the importance of bioinformatics
signaling pathway that is out of kilter,” Wardell
for developing curative therapies, the Myeloma
said. “We can get better answers to questions of
Institute has a dedicated team of five specialists,
diagnosis and treatment.”
including Wardell, who is the team leader. They
The more complicated the question, the more samples that are needed. Similarly, to determine
6
how frequently a certain gene is mutated, high-
are part of the first generation of full-time bioinformaticians, and they are poised to help
myeloma.uams
edu
the Myeloma Institute reach new heights in the
of cancer biology that will speed the
development of curative therapies.
development of precision medicine
“What makes us tick is reaching the clinic, feeling like you are making a difference,”
approaches to curing myeloma and related diseases.
Wardell said. While Wardell and two of his faculty colleagues are focused on the Myeloma Institute, their academic appointments are in the Department of Biomedical Informatics, established at UAMS one year ago. The department, directed by Fred Prior, Ph.D.,
Sources: American Medical Informatics Association, www.amia.org Kann, Maricel G: Advances in translational bioinformatics: computational approaches for the hunting of disease genes. Brief Bioinform. 2010 Jan; 11(1): 96-110. PMID: 20007728
develops computational tools to assess and manage medical and public health information and leverages data and maximizes its potential for improving health and health care. Prior is the principal investigator for The Cancer Imaging Archive (TCIA). Supported by the National Cancer Institute, the TCIA provides researchers, educators and the general public with a vast, freely accessible, open archive of cancer-specific medical images and metadata (http://www. cancerimagingarchive.net/). TCIA is a service
A lot of storage space is needed
that de-identifies and hosts a large archive
to accommodate the depth and
of medical images of cancer accessible for
volume of information. It is an
public download. The data are organized as
ever-growing challenge to store so
“Collections,” typically patients related by a
much data. Currently, the Myeloma
common disease (e.g. lung cancer), image
Institute’s data is stored both
modality (MRI, CT, etc.) or research focus.
on hard drives and in the cloud.
Prior’s group is in the process of hosting
Connections are encrypted and
radiology images, including PET and CT
very secure, and all data going to
scans, and gene expression data from the
the cloud is anonymized.
Myeloma Institute on TCIA. Both the Department of Biomedical Informatics and TCIA are valuable resources to the Myeloma Institute that help ensure that Wardell and his team have access to sophisticated, state-of-the art technology, information and processes. This, in turn, translates into expanded understanding
myeloma.uams
edu
7
Twenty Years and
Going Strong
Left to right: Patricia Harrison-Yates and Sonja Thornes
P
atricia Harrison-Yates has been a
green landscape and decided it was an
myeloma survivor for a very long
ideal, rural area to raise children. So, they
time. Twenty years, to be exact. She
packed up and moved. Harrison-Yates’
came to the Myeloma Institute in 1996,
in-laws, who had just retired, made the
underwent two transplants and has been
move with them.
doing well ever since. Originally from California, Harrison-
8
Life was good, with three children, involved grandparents and expansive
Yates moved to Joplin, Missouri, when
acreage of beautiful land. Harrison-Yates
she and her then-husband were ready
had a busy career and also pursued her
to start a family. During a visit with
passion for gardening by becoming a
relatives, they fell in love with the lush,
Master Gardener. myeloma.uams
edu
A diagnosis of myeloma hit Harrison-
customer services manager and a 25-
Yates when her kids were in college.
year employee, Harrison-Yates said,
Fortunately, the UAMS Myeloma
“When I had problems, Sonja took care
Institute was just a four-hour drive
of me.”
away. Not one to waste time, Harrison-
She was referring to insurance issues.
Yates was determined to face the
Harrison-Yates met Thornes on her first
myeloma head-on and get started with
visit to the Myeloma Institute, when
treatment. Her “can do” attitude was in
Thornes led the new patient intake and
high gear.
insurance division. They have been in
In addition to being enrolled in a
touch on a regular basis since then,
clinical trial for treatment, Harrison-
including the years when Harrison-
Yates also participated in a research
Yates was back in California and was
bone marrow and blood donation
followed by a physician there.
protocol for myeloma and related
Harrison-Yates has made special trips
“Pulling out a weed —
disorders; she has always had an
to Little Rock to attend two long-term
even just
interest in helping move the science
survivor celebrations at the Myeloma
one weed
forward. She has had more than 30
Institute – one in 2007 and one in 2012.
bone marrow biopsies done, all without
There was no way she was going to
— was my
any sedation. Her mindset is to “put on
miss the opportunity to gather with
your big boy pants” and do what has to
fellow patients and Myeloma Institute
be done.
doctors and nurses in the spirit of
At home between cycles of treatment, Harrison-Yates found solace and confirmation in the land. “Pulling out a weed — even just
thanks, gratitude and hope for a cure in
and grandchildren, all of whom are in the Joplin area, and travels extensively
physically close by when she was
(a trip to Puget Sound is coming up
undergoing treatment, they were able
next). By continuing to participate in
to follow her progress and provide
the research bone marrow and blood
support from a distance. Harrison-Yates
donation protocol, she is helping ensure
thinks that probably inspired them to
progress in developing treatments that
gravitate to health-related professions.
will bring a cure to many patients today
myeloma.uams
edu
was OK.”
she is cured. She enjoys each day,
everything was OK,” she said.
Thornes, the Myeloma Institute’s
everything
Harrison-Yates feels confident that cherishes her time with her children
Reminiscing recently with Sonja
that
the future.
one weed — was my validation that Although her children were not
validation
and in the future. In her words, “Life is good.” 9
Photo courtesy of Christer Berg
We Dig4
Crystals Cancer!
L
ast summer (2015) we shared with
help my family and me; it’s the least I
our readers a heartwarming story
can do,” she said.
about Bailey McNeill, 17 years old at
Before McNeill left home this fall for
the time, from Raleigh, North Carolina.
the University of North Carolina, Chapel
McNeill had created a web-based
Hill, Christer Berg, a local photographer
business, Crystals4Cancer.com, to sell her
doing a series on people making a
hand-crafted jewelry featuring crystals
difference in the area, captured this
from the North Carolina mountains.
image of her at the entrance to Randall
Fueled by a desire to help cure
Glen, the gem mine where she finds
myeloma, McNeill has been donating
crystals. We know that McNeill is indeed
half of the proceeds from her sales
making a difference and that she has
to support research at the Myeloma
tremendous strength of spirit and
Institute. “Though my contribution is
generosity. Berg definitely found a gem
small, I hope that my business is helping
in McNeill.
the program that has done so much to
10
myeloma.uams
edu
Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma A new publication in Blood (2016 Sep 29;128(13):1735-44, PMID: 27516441)
Primary Author: Niels Weinhold, M.D., Assistant Professor
Despite the introduction
performed the first longitudinal
oncogenes and complete
of novel agents, relapse
study that addressed the
inactivation of tumor
remains a challenge in
impact of a specific treatment.
suppressor genes, as well as
the treatment of multiple
(A longitudinal study is an
Darwinian-style evolutionary
myeloma. Understanding
observational research method
processes, as important
the underlying molecular
in which data is gathered for
contributors to myeloma cell
mechanisms of myeloma
the same subjects repeatedly
death resistance. The study
growth and relapse following
over a period of time; in this
emphasizes the benefit of
dose-intense chemotherapy
study at enrollment into a total
using alternate therapies with
could lead to new avenues of
therapy clinical trial and at
different action mechanisms
therapy aimed at overcoming
relapse.) Investigating gene
to induce myeloma cell death
these mechanisms. Dr. Gareth
expression, chromosomal and
and prevent relapse, especially
Morgan, Myeloma Institute
mutation profiles, Morgan’s
in high risk patients with an
director, and his research team
team identified activation of
inactivated TP53 gene.
myeloma.uams
edu
11
OUR BUDGET
FOR RESEARCH IS MORE THAN
$11.5 MILLION YOUR SUPPORT ENABLES US TO TURN RESEARCH BREAKTHROUGHS INTO LIFESAVING TREATMENTS This year, we ask you to lend your support for our research in precision medicine and targeted treatment approaches. Our talented team of scientists and clinicians is deciphering the molecular genetics of each patient’s disease and developing novel strategies for personalized therapies. With an unsurpassed repository of clinical and research data and dedicated bioinformaticians, we are uniquely positioned to conduct in-depth analyses on very large data sets, which in turn drive innovation in clinical applications. In addition, our collaborations with other international centers enhance our data by maximizing the scope of population variance. Genomic discovery across medical fields is progressing at an everincreasing rate. We are especially excited to propel this discovery in myeloma and related diseases.
12
myeloma.uams
edu
Expanding Molecular Genetics Expertise Brian Walker, Ph.D., professor and director of research at the Myeloma Institute since October 2015, heads up a team that is integrating gene expression profiling with DNA molecular profiling as a means of developing personalized treatments. Once a postdoctoral fellow himself, Sixty percent of our research funding comes from philanthropy. It is your
Walker has brought on board two new, talented Ph.D.s to help drive forward the research.
support that enables us to turn research
Samrat Roy Choudhury,
breakthroughs into lifesaving treatments
Ph.D., came to the Myeloma
for patients around the world. Every gift,
Institute from Purdue
no matter the size, advances the reality of cure.
University in Indiana, where
Thank you for making a difference.
research assistant with the
he was a postdoctoral
A remittance envelope is enclosed for your convenience. Or, you can donate online at http://myeloma.uams.edu/giving/. Annual Research Funding by Source
Department of Agricultural and Biological Engineering. His focus there was on epigenetic biomarkers in cancer cells and epigenomic toxicity of chemical compounds and engineered nanomaterials. Roy Choudhury received his Ph.D. in biotechnology and a master’s degree in zoology with cytogenetics and molecular biology, both from the University of Calcutta.
Philanthropy 60%
Aneta Mikulasova, Ph.D., joined the Myeloma Institute from Masaryk University in the Czech Republic with a background in molecular biology and genetics. The thesis topic of her recently earned doctoral degree was the prognostic
Grants and Other 40%
value of genetic abnormalities in monoclonal gammopathy of undetermined significance (MGUS).
myeloma.uams
edu
13
Left to right: Dr. Gareth Morgan, Owen Stephens and Dr. Niels Weinhold
Not by Chance: Eight NEW Genetic Risk Factors Discovered for Multiple Myeloma D r. Gareth Morgan, professor and director of
GWAS - Genome-wide Association Studies
the Myeloma Institute, Dr. Niels Weinhold,
Individuals with disease
Individuals without disease
assistant professor and director of genetics
GeneCh
GeneCh
at the Myeloma Institute, and colleagues from
Arabidop
sis ATH1
ip
Genome
Arabidop
sis ATH1
ip
Genome
Using a CHIP can genotype 5000,000 - 5 Million SNPs
Germany, the Netherlands, Sweden, Iceland, and the United Kingdom have identified eight
SNP 1
SNP 1 No association to disease
SNP 2
SNP 2 No association to disease
SNP 3
SNP 3 Associated to disease
additional gene variants that increase the risk of developing multiple myeloma. These results provide further evidence that multiple myeloma does not develop by chance, but is driven by inherited gene variants. The risk of developing multiple myeloma is increased in the relatives of individuals with multiple myeloma. In an international collaboration, the UAMS Myeloma Institute team investigated whether the cause for this increase may be found in the germline DNA* of patients. They analyzed characteristic changes in the
National Human Genome Research Institute, National Institues of Health
14
myeloma.uams
edu
genome of 9,866 patients and 239,188 healthy
Genome-wide association study
controls to identify inherited genetic variants
identifies multiple susceptibility loci
that are seen more often in multiple myeloma
for multiple myeloma
patients. Methodologically, they conducted a
Nature Communications 7, Article number:
meta-analysis** of genome-wide association
12050, published July 1, 2016
studies (GWASs)*** and investigated variations of single base pairs, so-called single nucleotide
*Germline DNA: the DNA in germ cells (egg
polymorphisms (SNPs). This largest GWAS to
and sperm cells that join to form an embryo).
date identified new risk loci that have relevance
Germline DNA is the source of DNA for all other
to myeloma biology. Locus (plural loci) refers to
cells in the body. Also called constitutional DNA.
the specific location of SNPs.
NCI Dictionary of Cancer Terms
While findings from the study provide evidence of inherited genetic susceptibility
**Meta-analysis: a systematic method that takes
to myeloma, further studies are needed to
data from a number of independent studies and
understand the biology behind the risk variants.
integrates them using statistical analysis.
These studies, conducted in coordination with
Dorland’s Medical Dictionary for Health Consumers
analyses of patients’ functional outcomes, are expected to lead to additional insights into
*** See pages 16-17
myeloma biology that support the development
Genome-wide association study https://www.genome.gov/20019523/genomewide-associationstudies-fact-sheet/
of new therapeutic agents and personalized medicine approaches to treatment.
Questions for Dr. Morgan and Dr. Weinhold
Q A
What is the primary significance of
risk. Therefore, they can only be detected in
this study?
data sets with several thousand cases and
genetic contributions to myeloma. Our findings have given us new insights into the early pathogenesis of multiple myeloma and are helping us develop new strategies to prevent myeloma.
Q A
controls.
We are really starting to hone in on the
Q A
Were the samples representative of most patients who are diagnosed with myeloma? Our samples came from a range of countries within Europe and from the United States and were representative of Caucasian
How important was the magnitude of the
patients. To investigate the impact of
study sample?
genetic variants on myeloma risk in patients
In contrast to the situation in other cancers, such as breast cancer where variants in BRCA1 and BRCA2 genes massively increase disease risk, genetic variants have only a small individual impact on multiple myeloma
myeloma.uams
edu
of African descent, we recently started a collaboration with Dr. Wendy Cozen, professor of preventive medicine at the University of Southern California. Results of this study will be presented soon.
15
Q A
Is it important to expand the study sample? Our calculations show that we have identified only a fraction of risk variants so far. Due to the small effect of these variants they are difficult to detect, but larger
Q A Q
Q A Q
Could this type of study be effectively
understanding of myeloma biology be
Yes. Does the information from this study have the potential to move forward Preventing myeloma is the ultimate goal. These findings are helping us develop appropriate strategies.
Q
Should a relative of a myeloma patient consider genetic testing for myeloma risk variants?
Will follow-up studies that lead to further conducted?
A
A
conducted at a single institution? Definitely not!
follow-up studies?
development of a myeloma cure?
cohorts will significantly increase the power to identify them.
Do you expect to be involved in these
A
While relatives have an increased risk of developing myeloma, their absolute risk is still very low. Thus, we do not recommend
Yes, we will be studying risk variants in
genetic testing for these variants.
myeloma plasma cells and model systems to identify their impact on cell biology.
Information about the Genome-wide Association Study from the National Human Genome Research Institute, National Institutes of Health
Q A
What is a genome-wide association
researchers now have a set of research
study?
tools that make it possible to find the genetic contributions to common diseases.
A genome-wide association study is an
The tools include computerized databases
approach that involves rapidly scanning
that contain the reference human genome
markers across the complete sets of DNA,
sequence, a map of human genetic variation
or genomes, of many people to find genetic
and a set of new technologies that can
variations associated with a particular
quickly and accurately analyze whole-
disease. Once new genetic associations
genome samples for genetic variations that
are identified, researchers can use the
contribute to the onset of a disease.
information to develop better strategies to detect, treat and prevent the disease.
Q A
Why are such studies possible now? With the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005,
16
Q A
How will genome-wide association studies benefit human health? The impact on medical care from genome-wide association studies could potentially be substantial. Such research is laying the groundwork for the era of myeloma.uams
edu
personalized medicine, in which the
along the inside of the mouth to harvest
current one-size-fits-all approach to
cells.
medical care will give way to more customized strategies. In the future, after improvements
genome, is then purified from the blood or cells, placed on tiny chips and scanned
are made in the cost and efficiency of
on automated laboratory machines. The
genome-wide scans and other innovative
machines quickly survey each participant’s
technologies, health professionals will be
genome for strategically selected markers
able to use such tools to provide patients
of genetic variation, which are called single
with individualized information about their
nucleotide polymorphisms, or SNPs.
risks of developing certain diseases. The
Q A
Each person’s complete set of DNA, or
If certain genetic variations are found to
information will enable health professionals
be significantly more frequent in people
to tailor prevention programs to each
with the disease compared to people
person’s unique genetic makeup. In
without disease, the variations are said
addition, if a patient does become ill, the
to be “associated” with the disease. The
information can be used to select the
associated genetic variations can serve
treatments most likely to be effective and
as powerful pointers to the region of the
least likely to cause adverse reactions in
human genome where the disease-causing
that particular patient.
problem resides. However, the associated variants
How are genome-wide association studies
themselves may not directly cause the
conducted?
disease. They may just be “tagging along”
To carry out a genome-wide association
with the actual causal variants. For this
study, researchers use two groups of
reason, researchers often need to take
participants: people with the disease being
additional steps, such as sequencing DNA
studied and similar people without the
base pairs in that particular region of the
disease. Researchers obtain DNA from
genome, to identify the exact genetic
each participant, usually by drawing a
change involved in the disease.
blood sample or by rubbing a cotton swab
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Questions? You can email us at myelomainstitute@uams.edu.
myeloma.uams
edu
17
An Active Outdoors Life Despite Myeloma
I
18
n July 2007, Jim Dykstra did a lot of
hot outside — 120 degrees. They also
hard-core hiking. With his brother
took long hikes in Bryce Canyon and
and nephew, he hiked to the bottom of
Zion National Park. Dykstra was 45
the Grand Canyon and back up. It was
years old and in great shape. Back-to-
a grueling three-day hike, and it was
back hikes were not a big deal for him. myeloma.uams
edu
The next month, home from the hiking
helping their mother and their uncle (Dykstra’s
adventures, Dykstra decided to get serious
brother) from Dallas. Dykstra’s son, at the age
about the nagging neck and shoulder pain
of 15, spent a week in Little Rock as the primary
that had stuck with him since an auto accident
caregiver during one of his father’s transplants.
the previous year. He wanted an answer to the
Dykstra is quite sure that his daughter’s decision
increasing numbness in his fingers, too. He had
to pursue a nursing career sprang, in part, from
been to a chiropractor and physical therapist,
her hands-on caregiving experience. She is
but the pain and numbness had persisted.
currently pursuing a doctorate in nursing at the
Finally, in October 2007, his insurance agreed
University of Wisconsin.
to cover an MRI, which revealed destruction of
A CPA by profession, Dykstra worked early
the seventh cervical vertebra (C7). An abnormal
in his career as a controller for Dole Food
M-protein level confirmed a diagnosis of
Company, traveling all over the world and living
myeloma.
in Costa Rica for six years. He and his wife, Jane,
Dykstra immediately made an appointment at
also a CPA, came back to the U.S. and settled
the Myeloma Institute. Coincidentally, his father
down in Incline Village to raise their family. They
had had myeloma, as well as colon cancer (his
quickly adapted to the magnificent environment
mother had colon cancer, too). Dykstra had
and its boundless opportunities for outdoor
done his homework about myeloma treatment
activities.
centers and knew all about the Myeloma
At the end of maintenance therapy, the last
Institute. What sold him without a doubt was
portion of the Total Therapy 3-like regimen,
the Myeloma Institute’s impressively large
Dykstra’s spirit of adventure and love of the
number of stem cell transplants and record of
outdoors and travel kicked back in. Anxious to
success.
resume an active lifestyle, even though tired
The first order of business was replacement
and a bit worn out, he retired from work and
of the damaged vertebra, performed by
resumed hiking, frequently with his dog and
UAMS neurosurgeon, Dr. T. Glenn Pait. Then,
always with Jane’s encouragement. He was
under the care of Dr. Frits van Rhee, Dykstra
determined to enjoy every day and live life to its
was treated on a regimen similar to the Total
fullest. Over time, his stamina returned.
Therapy 3 clinical trial. Treatment over a four-
Dykstra kayaks regularly on Lake Tahoe. In
year period included tandem transplants and
fact, this past July he completed his fifth five-
chemotherapy, some of which was done near
day trip around the 70-mile shore line. Two
his hometown of Incline Village, Nevada. When
years ago, at an altitude of 8,000 feet and
in Little Rock, he stayed at one of the hotels that
with more than 50 pounds on his back, he
provide shuttle service to/from UAMS. “Their
completed the 175-mile Lake Tahoe Rim Trail
staff understands,” he said.
that forms a loop around the Lake Tahoe Basin
Dykstra’s two children were in high school
in the Sierra Nevada and Carson ranges of
when he was diagnosed. They were exposed
California and Nevada. When he reached the
during their impressionable teenage years
150 mile mark, he was overcome with emotion.
to the realities of a cancer diagnosis and
Realizing that he would be able to complete the
treatment. They pitched in as caregivers,
journey in 15 days, he wept tears of thanks for
myeloma.uams
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19
“The doctors are hinting that they will
his renewed strength. Last summer
also retired, are back to traveling the
Dykstra completed a 170-mile, solo
world. Recent trips include Spain, the
trek along the John Muir Trail. “It was a
Caribbean, Hawaii, Alaska, and five
miracle,” he said. Never did he imagine
weeks in Europe.
during his four years of treatment that
Little Rock is on the travel list, too,
he would be able to get back to the
for annual checkup visits. Dykstra
outdoor adventures that he loves
always enjoys seeing his Myeloma
so much.
Institute family. “I can’t say enough
soon be able
Dykstra has a new appreciation
to declare me
for what he can do and how he can
talks with newly diagnosed patients,
help others. He readily shares his
he encourages them to come to Little
enthusiasm and joy for life. He is
Rock to get what he says is “the best
the vocabulary
active with Meals on Wheels through
care.” Nine years since diagnosis and
when I was
Sierra Senior Services. He is a regular
in complete remission, Dykstra has
diagnosed.”
with “Read with Me,” a program that
no detectable disease and has not
facilitates language and early literacy
received any treatment for the last
skills, with third-graders at the public
four and a half years. “The doctors
school. He coaches basketball for
are hinting that they will soon be able
middle school kids at the Incline
to declare me cured. That word was
Village Parks and Recreation Center.
not in the vocabulary when I was
And, Dykstra and Jane, who is now
diagnosed,” he said.
cured. That word was not in
20
about the staff,” he said. When he
myeloma.uams
edu
“Now you all find a cure for this Disease”
Cheryl and Owen Brown, standing center, with Cheryl's mother, seated, children and grandchildren
T
his is the message that accompanied a
focus on each and every patient. They felt
donation from Owen and Cheryl Brown of
confident that the obvious concern for the
Marietta, Georgia. Straight-forward and to-the-
whole patient would translate into personalized
point. Given, as was the donation, in the spirit
care within the context of a “let’s get going and
of helping all patients and their families who are
take care of this” spirit.
challenged by myeloma. When Cheryl Brown was diagnosed in 2015,
The Browns have been totally pleased with their choice. Cheryl’s no-nonsense, “if you can
she knew it was important to be treated
do this, I can do this” mindset has enabled her
by experienced specialists. Like so many
to tackle her treatment with confidence and
patients, she researched the options and was
weather the rough spots with resilience.
determined to identify a center with a proven
Cheryl feels very fortunate to have so much
record and an approach that best matched
to fight for — a loving husband, three children
her “can do” attitude. She and her husband,
and four grandchildren, all of whom live close-
Owen, visited a few facilities before settling
by. She also feels fortunate to be able to travel
on the Myeloma Institute. In addition to liking
to the Myeloma Institute for treatment. And,
the Myeloma Institute’s patient survival results
both she and Owen feel fortunate to be able
and novel treatment strategies, they were
to give back by supporting the research that is
impressed by the health care team’s sincere
improving the outlook for all patients.
myeloma.uams
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21
'All in' for Clinical Care Excellence
“Cancer patients are different from other kinds of patients. If they are going to seek treatment, they are all in.”
22
C
aring, Compassionate, Skilled. These adjectives describe
in health care administration. When Langster started her career
nurses that every patient wants at
in Canton, Illinois, fresh out of nursing
the bedside. They also apply to Holly
school, she was eager to learn the
Langster, the Myeloma Institute’s
ropes and become an accomplished
director of clinical operations, who
practitioner for her patients. Her
joined our team in July. An advanced
enthusiasm attracted the attention
practice nurse with more than 20
of an experienced charge nurse, who
years of nursing experience, Langster
“taught her how things were done.”
holds a Doctor of Nursing Practice, a
Langster took in everything and
degree that is focused on evidence-
quickly honed her skills. She learned
based practice, quality improvement
about managing a hospital unit, as
and systems leadership, and a master’s
well, and the importance of mentoring.
myeloma.uams
edu
Langster was particularly
administration and leadership roles at one of
struck by the benefits — for
the region’s medical complexes. When the
patients, families, and staff — of
director of clinical operations position at the
a comprehensive approach to
Myeloma Institute became available, Langster
patient care. She also was moved
knew she had to check it out. Comparing the
by witnessing her nursing mentor
Myeloma Institute to the Illinois breast center
go through tough treatment for
in its early days, Langster said, “The major
breast cancer and eventually
difference is that [at the Myeloma Institute]
succumb.
I was walking into something that’s already
It is no wonder that Langster
established, a well-oiled machine.” With the
jumped at an opportunity to join
Myeloma Institute’s ever-advancing research
an ambitious team in Springfield,
and development of personalized therapies, she
Illinois, that was embarking on
knew it was a place where she could make a
an exciting project: building a
difference.
dedicated breast center at the
Langster understands the complexities of an
Southern Illinois University Cancer
academic medical center and appreciates how
Institute (now called the Simmons
important it is to make sure that the Myeloma
Cancer Institute at SIU). The goal
Institute’s service line matches up with the
was to develop a one-stop center
overall mission and strategies of UAMS. She
that would provide integrated,
sees herself as a bridge builder, a resource
comprehensive services in an
finder, and a process improver. She wants
environment of compassion and
to make sure that “everything functions as
expertise. Langster helped make it happen.
effectively as possible.” With an emphasis on
Her years of experience with the breast center,
evidence-based practice and care pathway
where she functioned in both clinical and
tools, Langster is committed to high-quality
administrative roles, solidified her passion. She
health services delivered with compassion.
realized how much she enjoyed working with
“Every patient should immediately feel
cancer patients and ensuring that they received
welcome and safe,” she said.
seamless care. “Cancer patients are different from other
It is Langster’s charge to facilitate a system that helps the Myeloma Institute’s clinical
kinds of patients,” she said. “If they are going to
staff do their jobs efficiently, while keeping
seek treatment, they are all in. Cancer patients
the patient experience front and center. Her
place tremendous trust in their health care
passion and expertise are well aligned with
team. The information they get is complicated
her role. As the Myeloma Institute develops
and confusing. We need to be clear to them
precision medicine approaches for personalized
about what they need to do.”
care, Langster is reinforcing the basic nursing
Langster made the move from Illinois to
attributes of compassion and skill to maintain
Arkansas when her husband, originally from
the personal touch component that is integral
Arkansas, accepted an opportunity to return to
to overall excellence. Cancer patients are “all in”
his home state. Initially, she worked in nursing
and so is Langster.
myeloma.uams
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23
Non-Profit Organization US Postage
PAID
Little Rock, AR Permit No. 1973
4301 West Markham #816 Little Rock, AR 72205-7199
the scenes Michael Bauer, Ph.D. Bauer, an assistant professor of biomedical informatics, earned his doctoral degree in bioinformatics at the University of Arkansas at Little Rock (UALR). He holds a master’s degree in bioinformatics from UALR and a bachelor’s degree in biology and computer science from New Mexico Institute of Mining and Technology. Bauer is using advanced computational approaches for molecular profiling. Specific applications and emphasis focus on furthering the elucidation of multiple myeloma cancer biology through the development of custom software tools to integrate and validate molecular profiling data. Amy Buros, Ph.D. Buros, an assistant professor of biomedical informatics, earned her doctoral degree in statistical sciences from Baylor University in Waco, Texas. She holds a master’s degree in statistics and a bachelor’s degree in applied mathematics, also from Baylor. Buros is developing and improving statistical practices in clinical trials and has led the statistical analyses on multiple studies published in peer-reviewed journals, including the development of total lesion glycolysis in myeloma, a novel measure of both the number and intensity of focal lesions from PET/CT scans.