Myeloma Magazine | Fall 2016

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

Would you like to receive email updates from us?

Go to our website, www.myeloma.uams.

Note: if you already receive our email

edu, scroll to the bottom, and click on this

updates, you do not need to sign up.

button:

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

edu

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

edu

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

edu

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.