Spring 2010

Thank you for taking part in the Waldenström 

Macroglobulinemia (WM) Family Study. Our 

research team is truly grateful to you and your 

family members for taking part in this study. 

We appreciate the time and energy you gave 

to completing the questionnaires, giving us 

access to your medical records, and providing 

samples for our research. We hope that 

you will continue to assist us in this effort. 

So far, 116 families are taking part in 

this study, totaling 567 people. These 

include men and women with WM, their 

close family members, spouses and other 

relatives. Most participate from their home 

communities by filling out questionnaires 

and giving samples.

We would like to update you about our 

study activities and the scientific findings 

that you make possible. We hope that you 

will find the articles that follow informative.

If there are any topics or questions that 

you would like to see in future newsletters, or 

if you have questions about the information 

discussed in this newsletter or anything 

related to the study, please let us know. We 

welcome your phone calls, letters, or e-mails. 

Each of you has made a vital contribution 

to this research. Our research simply would 

not be possible without your willingness 

to take part in this study. Please accept 

our heartfelt “thank you” for all you have 

contributed to advancing our understanding 

of familial Waldenström macroglobulinemia. 

Mary L. McMaster, MD

Lead Investigator

The Problem of ‘Medicalese’ in WM

Wading through ‘Doctor Talk’

WM is a complex disease. Researchers and 

healthcare professionals have developed a 

complex language to describe it. We have 

found that our patients and their families 

usually know a lot about WM. However, 

it can often be hard to understand the 

language we use. We created a Glossary

to explain some of the terms that may be 

unfamiliar to you. Words or phrases that are 

underlined appear in the Glossary starting 

on page 15. Let us know if you have 

suggestions for other terms to include in

this list. The Resources and Links section 

lists excellent resources for patients and 

their family members who are trying to 

“learn the lingo.” 

The Power ofFamilies

WaldenströmMacroglobulinemia

FamilyStudyNewsletter

Division of Cancer Epidemiology and Genetics (DCEG)

WM Family Study Contacts:

Terri Giambarresi, R.N., Study Nurse Coordinator

Phone: 1-301-881-1460 or 

Toll-Free: 1-800-518-8474 

e-mail: theresegiambarresi@westat.com

Dr. Mary McMaster, Study Director

Phone: 301-496-4375

e-mail: Mary.McMaster@nih.hhs.gov 

Contents

 2 Study Findings

 6Related Research News

 8 Future Research

 9 Protecting Confidentiality

10Answers to Your 

Questions

National Cancer Institute

U.S. DEPARTMENT 

OF HEALTH AND 

HUMAN SERVICES

National Institutes 

of Health

WANT TO LEARN MORE?

If you would like more information on 

anything you have read in this newsletter, 

or on any aspect of the Waldenström 

Macroglobulinemia Family Study, please 

contact:

Terri Giambarresi

Phone: 1-301-881-1460 or 

Toll-Free: 1-800-518-8474 

e-mail: theresegiambarresi@westat.com

Dr. Mary McMaster

Phone: 301-496-4375

e-mail: Mary.McMaster@nih.hhs.gov 

Information about the NCI Genetic 

Epidemiology Branch may be found on the 

Web at http://dceg.cancer.gov/geb

NIH Publication No. 10-7520

Printed April 2010

Information about the NCI Genetic Epidemiology Branch may 

also be found on the Web at http://dceg.cancer.gov/geb

12Resources and Links

14 The WM Family 

Study Team

15 Glossary

19Medical Articles
Searching for WM Genes

Cytogenetics

Cytogenetics is the study of our chromosomes. 

Chromosomes are the 23 pairs of threadlike 

‘packages’ that hold all of our genes. 

Genes are made up of DNA. We can see 

chromosomes by looking at cells under a 

microscope. We sometimes see a break in 

a chromosome. This usually means that a 

particular piece of DNA has been damaged. 

Sometimes, these breaks can cause a 

cancer to develop. Cancer can also develop 

without a visible break. Since cancer cells 

are unstable, their chromosomes are more 

likely to break than the chromosomes in 

normal cells. In other words, sometimes a 

damaged chromosome can cause a cancer, 

and sometimes a cancer can cause damage 

to chromosomes. One of our challenges as 

researchers is figuring out which came first.

We know that many blood cancers 

(leukemia) and lymph node cancers 

(lymphoma) involve breaks in chromosomes. 

In certain leukemias, the chromosome 

breaks are so specific that they can be used 

to help diagnose the leukemia. Researchers 

have found some chromosome changes in 

WM cells. But these changes are not specific 

for WM. Researchers have not yet found a 

unique chromosome change that is present 

in WM cells in all patients. 

Researchers recently discovered that 

many – but not all – WM patients have 

damage to a particular chromosome. The 

damage causes loss (or deletion) of a piece 

of chromosome 6. This finding led scientists 

to ask whether damage to chromosome 

6 may be the first step leading to WM, 

including familial WM. 

Why is it Important to Know My Family‘s Medical History?

A family medical history is a record of health information about a person and his or her 

close relatives. A complete record begins with information from three generations of 

relatives, if available. Three generations of relatives include children, brothers and 

sisters, parents, aunts and uncles, nieces and nephews, grandparents, and first cousins. 

Many factors influence the development of complex disorders such as cancer. Families 

often share many of these factors. These factors may be genetic, environmental or lifestylerelated. Together, they can give clues to medical conditions that may run in a family. By 

reviewing family history, healthcare professionals may notice patterns of disorders among 

relatives. They can then determine whether an individual, other family members, or future 

generations may have a higher-than-usual chance of developing a particular condition.

If you have relatives with a medical condition, this does not mean that you will 

definitely develop that condition. A person with no family history of a disorder may still 

be at risk of developing that disorder. Knowing one’s family medical history may allow 

a person to take steps to lower his or her risk. 

The easiest way to get information about family medical history is to talk with your 

relatives about their health. Have they had any medical problems; if so, when did they 

occur? Getting copies of medical records and other documents (such as obituaries and 

death certificates) can help complete a family medical history. It is important to keep 

this information up-to-date and to share it with your healthcare professional regularly. 

There are many ways to record information about family history. The Department of 

Health and Human Services provides a private, internet-based tool to help individuals 

record and draw their medical family tree (called a pedigree). This tool, along with 

information about how to use it, may be found at https://familyhistory.hhs.gov.

Features of Familial WM

From studying 40 years of WM patient 

records, we have found that patients with 

familial WM are often diagnosed at a 

younger age than patients with sporadic 

WM. Many familial cancer syndromes 

share this feature. Young age at diagnosis 

suggests that a person’s genes may 

contribute to WM susceptibility. In some 

families, a parent and their child(ren) had 

WM. In other families, only brothers 

and/or sisters had the disease. These patterns 

are important because they provide us with 

clues about whether and how susceptibility 

to WM is inherited. 

In some families, relatives without WM 

had mild changes related to their immune 

system. These were usually minor changes 

in laboratory tests and caused no illness. 

Occasionally, the relatives had symptoms 

from an immune disorder. 

Some relatives also had high or low 

levels of immunoglobulin (a protein 

that helps the body’s immune system), 

including a condition known as monoclonal 

gammopathy.

We do not know whether these immune 

differences are more common in relatives 

of familial WM patients compared to the 

general population. They were not present 

in every family. When they occurred in a 

particular family, they were not present in 

every member of that family. We need to do 

more research to understand these findings. 

We would like to build upon the information we have about WM patients with and 

without a family history of the disease. We 

need to know about how WM behaves in all 

families, not in just some of them. 

How You Can Help The Study 

We are very interested in news about you and your family. If your 

family has had changes in address, births, new illnesses diagnosed 

or family members who have passed away, please let us know. 

Please complete and send back the enclosed “Family Update 

Form,” or contact our research nurse by phone or email. Each 

piece of information we receive from you brings us a little closer 

to understanding the mysteries of WM. We hope you will continue 

to help us by reporting your latest information and donating 

more blood, if needed. Our research cannot go 

forward without the help of families like yours.

You may reach the Study Team directly 

by using our contact information found at 

the bottom of page 1 and on the back cover of 

this newsletter.

Study Findings — What Are We Learning About Familial WM?

Patterns are 

important 

because they 

provide us 

with clues

2 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 3

We are very 

interested in 

news about you 

and your family. 
Candidate genes

The candidate gene approach searches for 

specific genes that might be related to the 

development of WM. Unlike a linkage study, 

in a candidate gene study we already have 

clues about which genes might be important. 

For example, we already know that some 

genes play a role in lymphoma or multiple 

myeloma, two conditions that are related to 

WM. We might expect that these genes play 

a role in WM as well. Another clue is finding 

chromosome breaks that occur within or 

very near specific genes that we know are 

important in bone marrow cells. 

Once we have chosen a candidate gene 

to study, we use DNA samples to look for 

changes in that gene in family members 

who have WM and those that do not. As a 

practical issue, studying candidate genes 

takes a lot of time, uses precious DNA, and 

is very expensive, so we want to choose 

the candidates very carefully. 

We recently studied a panel of candidate 

genes. The panel included genes that are 

involved in immune function, normal blood 

cell function, and inflammation. These genes 

have different forms (or alleles). We found a 

small group of genes that are more likely to 

appear in one form in WM patients and in a 

different form in their unaffected relatives. 

We do not believe that any of these genes, 

by themselves, cause WM. A change in 

any of these genes is likely to have a very 

small effect on risk for WM. However, they 

may act with other genes or environmental 

factors to influence susceptibility to WM. 

We are planning more studies to confirm 

our findings. 

Precursor Conditions for WM

We know that some types of cancer have a 

precursor condition. A precursor condition 

is a collection of unusual cells that are more 

likely than normal cells to develop into 

cancer. In the past, the only blood cancer 

known to have a precursor condition was 

multiple myeloma. The precursor condition 

for multiple myeloma is called MGUS or 

monoclonal gammopathy of undetermined 

significance. The hallmark of MGUS is the 

presence of an excess amount of a specific 

protein called immunoglobulin. The most 

common immunoglobulins are IgM, IgG, 

and IgA. IgM MGUS is related to WM. 

The MGUS protein related to myeloma is 

usually IgG or IgA.

At the beginning of the WM family study, 

we noticed that some of our patients’ healthy 

relatives had IgM MGUS but no sign of 

WM. When we looked very carefully, we 

could also find tiny amounts of IgM MGUS 

protein in other relatives and sometimes in 

healthy unrelated people. To learn more about 

this, we went back to data collected from 

our earliest participants and studied them 

in more detail. We found that if the amount 

of IgM MGUS was very small, it often 

disappeared over time. Among people who 

had a measurable amount of IgM MGUS, 

some but not all went on to develop WM 

after many years. We reported these findings 

at the Second International Waldenström 

Macroglobulinemia Workshop in 2002. Other 

scientists became interested in this topic and 

did more research of their own. 

We now know that IgM MGUS can be a 

precursor condition for WM. It is important 

to understand that precursor conditions do 

not always lead to cancer. In fact, precursor 

cells usually disappear with time. Cancer 

develops only if the precursor cells go 

through more genetic changes. For now, 

we cannot predict whether a person with 

IgM MGUS will go on to develop WM. 

This is an area of concern to many of our 

families. We are planning to continue to 

study it in detail and will keep you informed. 

We used cytogenetics to study bone 

marrow cells from patients in our study. 

We found chromosome damage in the cells 

of some familial WM patients. Most of 

these damaged chromosomes also occur 

in patients who have sporadic WM. The 

damaged chromosomes were usually 

different in each patient. This was true even 

in patients who were from the same family. 

Our conclusions were: 

•	 We did not find that deletions of 

chromosome 6 were more frequent 

in familial WM patients compared to 

patients with sporadic WM. 

•	 The chromosome changes found in 

familial WM appear to be similar to 

those found in non-familial WM. 

•	 Most importantly, we found no evidence 

that these particular chromosomal 

changes are inherited. 

Based on this research, we are looking for 

other ways to find susceptibility genes for WM.

Linkage study

An important way of searching for genes 

that might be involved in WM is called 

linkage analysis. In linkage analysis, 

researchers use statistics to study family 

and laboratory information. We use this 

information to look for locations on 

chromosomes containing genes that may 

be related to WM. We can only do linkage 

analysis if we have DNA from many WM 

families, including family members who 

have WM and those who do not have the 

disease. This is one reason why every 

member of every family that participates 

in our research is so important.

Linkage analysis is complicated. 

Researchers use genetic markers in DNA 

to follow the patterns of genes as they 

are passed from generation to generation 

or shared among relatives. We look for a 

change in the expected pattern. For example, 

we may look at the genes of many pairs 

of relatives with WM. If they share more

genetic markers in a particular region of 

a chromosome with each other than with 

their relatives who do not have WM, we 

say that WM is “linked” to that particular 

chromosome region. 

We conducted a linkage study using 

information from some of our WM families. 

We discovered that many people with WM 

shared genetic markers in four chromosome 

regions. These are our first clues about 

where to look for WM-associated genes. 

In future studies, we will be looking at 

ways to narrow these regions down. 

We will also be looking for more families 

with WM, since we want to know whether 

these regions are important in most WM 

families or only a few. 

A cell showing the 

packaging of DNA

into chromosomes 

within the cell’s 

nucleus. Genes occur 

along segments of a 

continuous strand, 

or molecule, of DNA. 

Altogether, genes 

carry the complete 

set of instructions 

for making all the 

proteins a cell will 

ever need. Separate 

strands of DNA are 

coiled into structures 

called chromosomes. 

4 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 5

We now 

know that 

IgM MGUS 

can be a 

precursor 

condition for 

WM.
Risk Factors for WM

We knew from earlier population-based 

studies that the risk of developing WM is 

related to age and gender. WM is more 

likely to develop with increasing age and 

is more common among men. 

Those same studies suggested that WM 

risk might also be related to race, because 

WM is more than twice as common in whites 

as in African-Americans. However, very 

little was known about other factors that may 

increase the chance for a person to develop 

WM. Our research has added to what we 

know about the potential risk factors for WM.

Influence of Race on Risk for WM

Studies done in the 1990s showed us that 

in the U.S.:

•	 African-Americans are only half as 

likely as whites to develop WM. 

•	 But they are twice as likely as whites 

to develop multiple myeloma, a related 

cancer.

These differences could be due to genetic 

factors, or they could be due to differing 

environmental exposures. 

If environmental exposures are important, 

then we might see differences between 

African-Americans and Africans. We tested 

immunoglobulins in over 900 African men 

in the country of Ghana. We then compared 

their results to those from white men in the 

U.S. We found that African blacks are nearly 

twice as likely as U.S. whites to have the 

precursor condition of multiple myeloma, 

called MGUS (monoclonal gammopathy of 

undetermined significance). This is similar 

to the pattern for blacks and whites in the 

U.S. We then looked at the specific type of 

MGUS (IgM MGUS) that we have found 

to be a precursor condition for WM. (See 

Precursor Conditions for WM on page 5.) 

We found IgM MGUS in only 6% of African 

blacks, compared to 14% of U.S. whites. 

In other words, African blacks and AfricanAmericans appear to have similar patterns 

of both MGUS overall and IgM MGUS 

compared to whites. While this finding does 

not explain why blacks in the U.S. seem to 

be less likely than whites to develop WM, 

it does suggest that there may be factors 

related to race that influence susceptibility 

to WM. 

We work with researchers around the world 

who are interested in WM and related 

blood and lymph node cancers. Below is a 

summary of some of the other research that 

we are doing to better understand WM.

Studies of WM and B-cell Cancers 

in the General Population

What is a B-cell? 

Our blood contains many different types 

of cells. Each type of cell has a special 

job to keep us healthy. One special type of 

blood cell is the B-lymphocyte or B-cell. 

B-cells are important in immune function. 

A healthy immune system allows us to 

fight infections and to rid our bodies of 

diseased cells. B-cells pass through several 

stages as they mature. Most of the time, 

B-cells are on ‘stand-by’ in our blood, 

lymph nodes and bone marrow. However, 

when germs invade our bodies, B-cells 

are ‘activated.’ An activated B-cell begins 

making large amounts of antibodies (also 

called immunoglobulins) to fight the germs 

or diseased cells. 

Is WM a type of B-cell cancer? 

Yes. Although relatively rare, a cancer 

can arise from a B-cell at any stage of its 

development. WM affects B-cells that 

have almost completely matured. Other 

cancers that affect B-cells at different 

stages of their development include chronic 

lymphocytic leukemia (or CLL), multiple 

myeloma, Hodgkin lymphoma, and many 

types of non-Hodgkin lymphoma. These 

cancers are related, even though each has 

special features. Researchers are working 

to understand more about how these 

cancers are related.

Do relatives of WM patients have a higher-than 

usual chance of developing WM or a related 

B-cell cancer? 

Yes, we have found that relatives of patients 

with WM had a higher-than-usual chance 

of developing WM as well as two other 

related B-cell cancers, called non-Hodgkin 

lymphoma and chronic lymphocytic 

leukemia. 

WM and other B-cell cancers are rare.

Even though relatives have a higher-thanusual chance of developing them, the overall 

chance remains low. For example, CLL is 

about 20 times more common than WM. 

The lifetime chance for any person to 

develop CLL is less than 1 in 100. Although 

a close relative of a WM patient is about 

two times more likely to develop CLL than 

someone who is not related to a WM patient, 

the chance is still less than 1 in 100. 

Related Research News

Chronic Immune Stimulation and Risk for WM

We studied over 4 million U.S. veterans who were hospitalized in 

VA hospitals during a 27-year period (1969 – 1996). We identified 

patients who were diagnosed with WM and compared them to 

veterans who were not diagnosed with WM. For both groups, 

we collected information about autoimmune diseases, allergic 

conditions, and a variety of infections. We found that patients who 

developed WM were more likely to have had a prior history of 

autoimmune disease or certain infections, but not allergies. These 

findings do not mean that autoimmune diseases or infections 

cause WM. They do give us some ideas about important 

biological mechanisms that we hope to evaluate further. 

We work with 

researchers around 

the world who are 

interested in WM and 

related blood and 

lymph node cancers.

WM is more 

likely to 

develop with 

age and is 

more common 

among men.

We studied over 4 million 

U.S. veterans who were 

hospitalized in VA hospitals 

during a 27-year period 

(1969 – 1996).

6 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 7

Colored scanning electron 

micrograph of a lymphocyte. 

Lymphocytes are a type of 

white blood cell involved 

in the immune system. 

Lymphocytes are divided 

into either B-cells or 

T-cells. B-cells mature in 

the bone marrow and are 

responsible for antibody 

(or immunoglobulin) 

production, including IgM.
Lessons from the Questionnaires

We are now analyzing the data that you 

provided in your questionnaires when 

you first enrolled in the study. We hope to 

use this information to learn more about 

the WM disease process when there 

is a family history of WM by finding 

answers to questions such as: 

•	 If you have a family history of WM, 

are you likely to have the same kinds 

of symptoms as someone without a 

family history? 

•	 Is your WM more or less likely to need 

treatment early? 

•	 Are there any conditions or exposures 

that occur more often in family members 

with WM than in unaffected family 

members? 

We hope to have answers to these questions 

soon.

Lessons from Lab Tests

When you donate blood and urine samples 

for the WM family study, we use some of 

the samples for clinical testing. We send the 

results of that testing back to you along with 

our interpretation and recommendations, if 

applicable. We also use some of the samples 

for research laboratory tests. We now 

have enough data to begin to analyze the 

laboratory tests. We are currently working 

with statisticians to develop the analysis plan 

and expect to begin the analysis soon. Our 

goal is to see if family members who do not 

have WM have other features in common. 

We plan to publish our results in a scientific 

journal. If we learn anything that has clinical 

importance for you, we will also share the 

information with you directly. 

Lessons from Genetic Analyses

We were very excited by the results of our 

first linkage study (see Linkage study on 

page 4). We identified four regions of the 

genome that may contain WM susceptibility 

genes. Each region is very large and contains 

hundreds of genes. Studying every gene in 

these regions is not practical, so we want 

to confirm our results before we start a 

detailed analysis. 

Fortunately, WM families are continuing 

to enroll in this study. We are planning a 

larger linkage study focusing on families 

that have more than two members with WM. 

By focusing on larger families, we will have 

greater confidence in our results. In addition, 

because there are more people with WM in 

these families, we expect that any WM genes 

will be more common and hopefully easier 

to find. We are also excited because this 

linkage study will be an international effort. 

One of our goals is to foster successful 

teamwork among scientists worldwide.

Future Research — Where Do We Go From Here? How Do We Protect Your Rights and Confidentiality?

Patients sometimes ask us what procedures we have in place to protect their confidentiality. 

They may be concerned about their ability to obtain insurance in the future. Others may 

prefer to keep information about their diagnosis private, even within their family. Still 

others may wonder who has access to their samples and for what purpose. 

Protecting your privacy is our utmost concern, so we want to share with you more details 

of how the NCI handles your information and samples: 

•	 When we first design a study, we describe how we will protect our participants’ privacy. 

We also make every effort to list the specific uses we intend for the samples and to give 

scientific reasons why lab studies are necessary. All of our study plans are reviewed by 

the NCI’s Institutional Review Board (IRB). The IRB is made up of scientists, doctors, 

clergy, and consumers from both within and outside NCI. The IRB reviews the study 

procedures annually and has the right to stop the research if it believes the risk to the 

participants is too high, the participants’ privacy is not adequately protected, or the 

scientific reasons are not sound. 

•	 At the beginning of a study, each participant signs an informed consent form. This form 

describes the study and outlines possible uses of samples in the future. Those who take 

part in the study can allow or decline use of their samples for these purposes. If we 

find new uses for your samples beyond those listed in the study design or consent form, 

then we must bring new proposals to the IRB for review and approval.

•	 We collect samples and store them in a special laboratory to keep them in a stable 

condition. These are closely-guarded, highly-secure facilities. All samples are given a 

code number and do not carry your name or other identifying information. The only 

people who can make the connection between the code and your personal data are those 

NCI staff who are directly involved in this specific study. 

•	 The study has a Certificate of Confidentiality, which protects researchers and/or institutions 

from being compelled to disclose any information that would identify study participants, 

thereby protecting the privacy of research participants. The researchers involved in 

this study have pledged to keep all information confidential. For more information on 

Certificates of Confidentiality, please visit http://grants2.nih.gov/grants/policy/coc/.

•	 Because the purpose of our research is to increase understanding of WM, it is important 

for us to share our research results with the scientific community. This is usually done 

by presenting our results at scientific meetings or preparing articles for publication 

in scientific journals. We will not identify you individually in any publication or 

presentation resulting from this study. 

Our study is part of the research program of the Genetic Epidemiology Branch (GEB) within 

the National Cancer Institute’s (NCI) Division of Cancer Epidemiology and Genetics (for more 

information about who we are and the work we do, please visit http://dceg.cancer.gov/). NCI is 

part of the National Institutes of Health, the Federal Government’s biomedical research agency.

Our goal is to learn as much as we can about familial WM as quickly as possible, without 

placing you or your privacy at risk. 

Your samples are an incredibly valuable gift to science and the community at large. 

Thank you again for your remarkable generosity.

All samples 

are given 

a code 

number and 

do not carry 

your name 

or other 

identifying 

information. 

8 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 9
Are Other Cancers Associated with WM?

There are two parts to this question. First, is a 

patient with WM more likely to be susceptible to 

other cancers? We do not yet know the answer 

to this question. Studies with a large number of 

patients are needed to further evaluate this question.

The second part of this question is whether the 

relatives of a WM patient are susceptible to WM 

or other cancers. We have some information about 

other blood and lymph node cancers in family 

members of WM patients. We recently found that, 

if a person is diagnosed with WM, then his/her 

close relatives (parents, siblings, and children) are 

at slightly increased risk for chronic lymphocytic 

leukemia and non-Hodgkin lymphoma. See 

Research News on page 6 in this issue for more 

information about this finding.

How Much do Environmental Factors Affect WM?

We do not yet know the answer to this question. 

We hope to get some clues from our analysis of your 

questionnaire information. Some recent studies 

(see Research News) have looked at infections prior 

to WM. They found that patients with WM were 

more likely to have had certain infections, such as 

hepatitis C and HIV, the virus that causes AIDS, than 

patients without WM. That does not mean that these 

infections cause WM. It is more likely that there is 

some common link between these infections and 

WM, such as problems with the immune system. 

Can WM be Prevented?

Until we know what causes WM, we can only have 

an educated guess about what might help prevent it. 

Data suggest that immune function may be related 

to WM. WM can also cause problems with immune 

function, so it can be hard to tell which comes first. 

There are steps you can take to encourage a healthy 

immune system. These include:

•	 Choose healthy foods 

•	 Get regular exercise 

•	 Get plenty of sleep 

•	 Practice stress-reduction strategies 

•	 Avoid tobacco products

•	 Practice sun safety; avoid sunburns 

Are There Foods that Increase Blood Counts?

Low blood cell counts in WM are usually caused 

by the WM cells ‘crowding out’ the normal bloodforming cells in the bone marrow. Also, the IgM 

can sometimes attack the blood cells and cause low 

blood counts. When low blood counts are due to 

these effects of WM, specific foods are not likely 

to increase the blood counts. Instead, the low blood 

counts are usually a very good reason to treat WM. 

Successful treatment of WM often allows the blood 

counts to recover. 

Nutrition may influence certain types of blood 

counts. Low red blood cells (called anemia) may be 

due to iron deficiency or deficiency of other specific 

nutrients such as folate or vitamin B12. Consult 

your healthcare provider if you have anemia from 

one of these causes and discuss which foods are 

likely to be beneficial. 

Is There a Web Site that Lists Ongoing 

Clinical Trials for WM? 

The NCI maintains a web site that contains fully 

searchable information about every NCI-sponsored 

clinical trial for WM and other cancers. It can be 

accessed at: http://www.cancer.gov/clinicaltrials/

search/ (See Resources and Links).

For questions, please feel free to contact us at: 

Terri Giambarresi, R.N.

Phone: 1-301-881-1460 or 

Toll-Free: 1-800-518-8474 

e-mail: theresegiambarresi@westat.com

Dr. Mary McMaster

Phone: 301-496-4375

e-mail: Mary.McMaster@nih.hhs.gov 

What is MGUS? 

‘MGUS’ stands for ‘monoclonal gammopathy of 

undetermined significance’. IgM is one type of 

special blood protein called an immunoglobulin, 

or antibody. Immunoglobulins are made by a 

type of specialized white blood cell called a 

‘B-lymphocyte’ or ‘B-cell’. All IgM molecules 

share similar features. However, the IgM made 

by a given B-cell will have very small differences 

from the IgM made by all other B-cells. Usually, 

IgM is constantly produced at a low level by many 

millions of B-cells. This normal IgM is called 

polyclonal (‘poly’ means ‘many’ and ‘clonal’ 

refers to cells). Sometimes, a B-cell makes 

identical copies of itself. Then, all these identical 

B-cells (called a ‘clone’) will make identical IgM 

molecules. When this happens, an excess of IgM 

develops. The condition of having excess identical 

IgM molecules is called ‘monoclonal gammopathy’ 

(‘mono’ means ‘one’ and ‘gammopathy’ refers 

to atypical immunoglobulins). If there is enough 

monoclonal protein, then we can identify and 

measure it using a laboratory test called protein 

electrophoresis. This is sometimes called the 

“M-spike” because of how it looks on the 

laboratory test result.

By itself, monoclonal gammopathy doesn’t 

tell us much. Many conditions can cause B-cells 

to make excess immunoglobulin. For example, 

certain inflammatory conditions, infections, 

autoimmune disorders and drug reactions may 

be associated with a monoclonal gammopathy. 

Sometimes, a cause for the monoclonal 

gammopathy cannot be found. When we can 

find no cause for the monoclonal gammopathy, 

we say that it is of unknown or ‘undetermined’ 

significance. We then call it MGUS. 

MGUS occurs in about 3% of healthy adults. 

It becomes more common as we age. MGUS is 

very rare under age 30 and is thought to occur in 

10% or more of people at age 80. In most cases, 

MGUS disappears or stays the same over time. 

This is especially true when there is only a small 

amount of the MGUS protein. If the MGUS 

persists, a small number of individuals with it will 

develop a blood or lymph node cancer. Most people 

with MGUS never develop any serious disease. 

However, a small number of individuals with IgM 

MGUS may develop WM, chronic lymphocytic 

leukemia, or another non-Hodgkin lymphoma. 

At What Age is WM Usually Diagnosed? 

The “typical” WM patient is diagnosed at about age 

70. If you read medical articles about WM, you will 

often see a younger average age quoted, usually 

63 – 65 years. Remember that most medical articles 

come from universities that are reporting on the 

patients in their clinical trials. Older patients may 

be less likely to participate in clinical trials and so 

would not be included in these articles.

What Part(s) of the Body Does WM 

Usually Affect?

By definition, WM affects the bone marrow, 

although the WM cells may be hard to find early in 

the disease. The next most common areas are lymph 

nodes and spleen. WM tumor cells can sometimes 

be found in unusual locations, such as around the 

eye or in the intestinal tract, lungs or skin. 

WM is unique among cancers in that symptoms 

can be caused by either the WM cells or the IgM 

protein. The IgM protein circulates in the blood. 

Since blood travels to every part of the body, 

then it is possible to have IgM-related symptoms 

anywhere. IgM can cause symptoms in two ways: 

1) because of its size, and/or 2) because it is an 

antibody. Most IgM-related symptoms that are due 

to the size and/or “stickiness” of the IgM protein are 

part of the hyperviscosity syndrome. Because it is 

an antibody, IgM can cause symptoms by attacking 

body tissues by mistake. Peripheral nerves (that 

is, nerves outside the brain and spinal cord) and 

various blood cells are the most common targets of 

mistaken IgM attack. Patients with peripheral nerve 

involvement may experience numbness or a painful 

or burning sensation in their feet or hands. If blood 

cells are targeted, patients may develop a low red 

blood cell count, called anemia or a low platelet

count, called thrombocytopenia. 

Answers to Your Questions

10 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 11
Non-Federal Sites*

American Cancer Society: 

http://www.cancer.org

The American Cancer Society (ACS) 

provides information and resources for 

cancer patients nationwide, as well as 

funding for clinical and basic research in all 

aspects of cancer biology and treatment. 

American Society of Clinical Oncology: 

http://www.cancer.net

The American Society of Clinical Oncology 

(ASCO) provides oncologist-approved 

information and resources for cancer patients 

and their caregivers. It includes information 

on national policy, guides to specific cancer 

types, and resources for understanding and 

managing costs of cancer care and coping 

with the impact of a cancer diagnosis.

International Waldenström Macroglobulinemia 

Foundation (IWMF): 

http://www.iwmf.com

IWMF provides information, resources, a 

communications network, and experience 

on how to live with WM, as well as mutual 

support among individuals who have WM 

and their caregivers. There are members 

and local area support groups worldwide. 

IWMF sponsors an annual patient education 

forum each spring. IWMF also encourages 

and funds research toward more effective 

treatment of WM.

Federal Government Sites

National Cancer Institute Information Line: 

http://www.cancer.gov

1-800-4-CANCER

This resource, sponsored by the National 

Cancer Institute (NCI), provides information 

on current research for a variety of cancer 

sites. It provides a searchable index of all 

NCI-supported clinical trials for WM and 

other cancers. It also discusses a variety 

of cancer-related topics in lay terms. It 

is an excellent resource for patients and 

oncologists who wish to explore the 

availability of clinical trials testing new 

treatments for different cancers.

National Human Genome Research Institute: 

http://www.genome.gov/Education/ 

The National Human Genome Research 

Institute (NHGRI) is a component of the 

National Institutes of Health. NHGRI 

maintains an Educational Resources page 

on its web site that is devoted to providing 

information about concepts related to 

genetics, a glossary of genetic terms, and 

more. While not strictly related to WM, 

it provides a user-friendly way to learn 

about the general topic of genetics.

PubMed Central: 

http://www.pubmedcentral.nih.gov/

PubMed Central, a service of the National 

Institutes of Health (NIH), provides free 

digital archives of biomedical and life 

sciences journal literature. A search of 

PubMed Central will provide the citations 

for relevant publications. The citation may 

contain a link to the actual article if the 

publisher has agreed to make the article 

available to the public.

My Family Health Portrait 

https://familyhistory.hhs.gov/

My Family Health Portrait is a web-based 

tool that makes it easy for you to record 

your family health history. The tool allows 

you to assemble your information and 

makes a “pedigree” family tree that you can 

download to share with family members or 

your healthcare practitioner. The Web site 

only provides the software for organizing 

your information. By accessing the tool on 

the web, you make use of that software. The 

information you fill in is never available to 

anyone else, unless you decide to share it. 

Resources and Links

*We are providing links to other Internet 

sites for informational purposes and 

for your convenience. Please note the 

following:

1. When you select a link to an external 

Web site, you are leaving the NCI 

Web site and you are subject to the 

privacy and security policies of the 

owners/sponsors of the external site.

2. NCI does not endorse organizations 

that sponsor linked external Web 

sites. In addition, NCI does not 

endorse products or services that such 

organizations may offer. Furthermore, 

NCI does not control or guarantee 

the currency, accuracy, relevance, 

or completeness of information found 

on linked, external Web sites.

3. NCI is not responsible for 

transmissions users may receive from 

linked, external Web sites.

4. NCI does not guarantee that linked, 

external Web sites comply with 

Section 508 (Accessibility Requirements) of the Rehabilitation Act.

We are providing

links to other 

Internet sites for 

informational 

purposes and for 

your convenience. 

12 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 13
We have provided a list of definitions of some of 

the genetic and technical terms that will make 

this newsletter easier to understand.

affected – An individual in a pedigree or family 

who has the condition that is being studied.

allele – An allele is one of two or more versions of a 

gene. An individual inherits two alleles for each gene, 

one from each parent. If the two alleles are the same, 

the individual is homozygous for that gene. If the 

alleles are different, the individual is heterozygous. 

Different alleles produce variation in inherited 

characteristics such as hair color or blood type. 

anemia – A condition in which the number of 

red blood cells is below normal. Red cells are the 

cells that carry oxygen from the lungs through the 

bloodstream to other organs throughout the body.

autoimmune disease – A condition in which the 

body mistakenly recognizes its own tissues as foreign 

and directs an immune response against them. 

Patients with autoimmune diseases frequently have 

unusual antibodies circulating in their blood that 

target their own body tissues. 

autosomal – Refers to any of the chromosomes 

numbered 1 – 22 or the genes on chromosomes 

1 – 22. This term excludes the sex-determining 

chromosomes, X and Y. 

benign – A tumor that grows but does not invade 

nearby tissues or spread to distant tissues.

B-lymphocyte – (see lymphocyte)

cancer – A term for diseases in which abnormal cells 

divide without control and can invade nearby tissues. 

Cancer cells can also spread to other parts of the 

body through the blood and lymph systems. There are 

several main types of cancer. Leukemia is a cancer 

that starts in blood-forming tissue such as the bone 

marrow and causes large numbers of abnormal blood 

cells to be produced and enter the blood. Lymphoma 

and multiple myeloma are cancers that begin in the 

cells of the immune system. Also called malignancy.

cancer screening – Checking for disease when there 

are no symptoms. Since screening may find diseases 

at an early stage, there may be a better chance of 

treating the disease. Examples of cancer screening 

tests are the mammogram (breast), colonoscopy 

(colon), Pap smear (cervix), and PSA blood level 

and digital rectal exam (prostate). Screening can also 

include checking for a person’s risk of developing 

an inherited disease by doing a genetic test.

candidate gene – A candidate gene is a gene whose 

chromosomal location is associated with a particular 

disease or other phenotype. Because of its location, 

the gene is suspected of causing the disease or other 

phenotype.

chromosome – One of the threadlike “packages” 

of genes and other DNA in the nucleus of a cell. 

Except for sperm and eggs, all human cells contain 46 

chromosomes that occur in 23 pairs: 2 pairs of each 

of the 22 autosomes, plus either two X chromosomes 

(females) or an X and a Y chromosome (males). 

clone – Cells that are derived from a single common 

ancestor cell. Clonal cells are a group of cells of the 

same type that are genetically identical. Cells from a 

single clone are called monoclonal.

cytogenetics – The study of chromosomes and 

chromosomal abnormalities.

deletion – The loss of all or a part of a gene. There 

may also be a change in the RNA and protein 

made from that gene. Certain gene deletions are 

found in cancer and in other genetic diseases and 

abnormalities.

disease-causing mutation – A gene change or 

alteration that causes or predisposes an individual 

to develop a specific disease.

DNA – The molecules inside cells that carry genetic 

information and pass it from one generation to the 

next. Also called deoxyribonucleic acid.

electrophoresis – A laboratory test used to separate 

substances, such as proteins, based on the rate of 

movement of each component while under the 

influence of an electric field. Proteins can be identified 

because they move at a predictable rate based on their 

physical and electrical properties. Electrophoresis 

is commonly performed on serum or urine. After 

the proteins have been separated, they are identified 

using special stains. There are two major methods 

used for this process, immunoelectrophoresis and 

immunofixation electrophoresis.

epidemiology – The study of the patterns, causes, and 

control of disease in groups of people.

familial cancer – Cancer that occurs in families 

more often than would be expected by chance. These 

cancers often occur at an early age and may indicate 

the presence of a gene mutation that increases the risk 

of developing cancer. They may also be a sign 

of shared environmental or lifestyle factors.

Mary L. McMaster, M.D., is the Lead 

Investigator of our study. Dr. McMaster 

is responsible for developing and leading 

the study. She trained in medical oncology 

at Vanderbilt University and in medical 

genetics at the National Human Genome 

Research Institute before coming to the 

National Cancer Institute (NCI). She is an 

expert in familial WM and WM precursor 

disorders. She has been studying patients 

with familial WM for over 10 years. She 

was a founding member of the International 

Waldenström Macroglobulinemia Workshop 

in 2000. She has also worked closely 

with the International Waldenström 

Macroglobulinemia Foundation to raise 

awareness about familial WM. 

Terri Giambarresi, B.S.N., R.N., G.C.N., is 

our primary Research Nurse. She is your first 

line of communication and information about 

the study. Terri will work with you on putting 

together your family history information 

and in organizing visits to our clinics and 

coordinating medical tests.

Linda Vasquez, A.A., R.N., is a Clinical 

Research Specialist who assists Terri and 

Dr. McMaster in coordinating all the details 

of the study. Along with Terri, Linda assists 

patients and family members who come 

to the NIH Clinical Research Center for 

evaluation.

Lynn Goldin, Ph.D., is a Genetic 

Epidemiologist on the study. Dr. Goldin 

trained at the University of North Carolina 

at Chapel Hill. Her major research interests 

are in developing and evaluating statistical 

methods and study designs for detecting 

susceptibility genes for complex diseases, 

quantifying how diseases cluster in families, 

and applying these methods to familial 

cancer studies.

The Waldenström Macroglobulinemia Family Study Team

Comings and Goings

Deborah Colby, M.A., has assumed the 

role of Research Assistant for the study. She 

has a B.A. in psychology from the University 

of Maryland, Baltimore County and an M.A. 

in experimental psychology from Towson 

University. She helps the study to run smoothly 

by assisting Terri and Linda and maintaining 

and managing study records.

Jill Koshiol, MSPH, Ph.D., has joined the 

study team as a Cancer Epidemiologist. 

Dr. Koshiol trained in epidemiology at the 

University of North Carolina at Chapel Hill. She 

is interested in infections that cause cancer. 

She is particularly interested in why immunerelated conditions, such as certain autoimmune 

diseases and infections, seem to increase risk 

of WM. 

Ruth Pfeiffer, Ph.D., has joined us as our 

study’s Statistician. She is helping us develop 

the statistical methods for our new analyses. 

Dr. Pfeiffer received her Ph.D. in mathematical 

statistics from the University of Maryland, 

College Park. Her research focuses on 

statistical methods for problems arising in 

genetic epidemiology.

Ola Landgren, M.D., trained in hematology 

and internal medicine at the Karolinska 

Institute (Stockholm, Sweden). In 2004, he 

came to the National Cancer Institute, 

Genetic Epidemiology Branch, DCEG, where 

he worked as an Investigator before he 

joined NCI’s Medical Oncology Branch. His 

research interest is in the natural history of the 

precursor condition, monoclonal gammopathy 

of undetermined significance (MGUS), and its 

relationship to WM. We collaborate with him 

on various aspects of the study.

Veda Byrd, B.S., who worked with many of 

you in the study, left the NCI to enter a graduate 

program in public health. We know that you join 

us in wishing her the best of luck in her studies.

Glossary — Words to Know

14 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 15
linkage – The close association of genes or other 

DNA sequences on the same chromosome. The closer 

two genes are to each other on the chromosome, the 

greater the probability that they will be inherited 

together.

linkage analysis – A gene-hunting technique that 

traces patterns of disease in high-risk families by 

identifying genetic markers of known chromosomal 

location that are inherited along with the trait or 

disease of interest. 

lymphocyte – A type of immune cell that is made 

in the bone marrow and is found in the blood and in 

lymph tissue. The two main types of lymphocytes 

are B-lymphocytes (also called B-cells) and 

T-lymphocytes. B-lymphocytes make antibodies, 

and T-lymphocytes help kill tumor cells and help 

control immune responses. A lymphocyte is a type 

of white blood cell.

lymphoma – Cancer that begins in cells of the 

immune system. There are two basic categories 

of lymphomas. One kind is Hodgkin lymphoma, 

which is marked by the presence of a type of cell 

called the Reed-Sternberg cell. The other category 

is non-Hodgkin lymphoma, which includes a large, 

diverse group of cancers of immune system cells. 

Non-Hodgkin lymphomas can be further divided into 

cancers that have an indolent (slow-growing) course 

and those that have an aggressive (fast-growing) 

course. These subtypes behave and respond to 

treatment differently. Both Hodgkin and non-Hodgkin 

lymphomas can occur in children and adults, and 

prognosis and treatment depend on the stage and the 

type of lymphoma.

malignancy – Another term for cancer. A malignant 

tumor can invade nearby tissues and has the ability to 

spread to distant tissues through the bloodstream or 

lymph system. 

mode of inheritance – The manner in which a 

genetic trait or disorder is passed from one generation 

to the next. Autosomal dominant, autosomal 

recessive, X-linked dominant, X-linked recessive, 

multifactorial, and mitochondrial inheritance are 

examples. Each mode of inheritance results in a 

characteristic pattern of affected and unaffected 

family members.

monoclonal – A group of cells that are all identical 

copies of an original cell. Such a population of 

identical cells is called a clone, and monoclonal 

means a single clone. All tumors, both benign and 

malignant, are monoclonal, that is, they are the result 

of the transformation of a single cell. That single cell 

multiplies and forms the tumor. 

monoclonal gammopathy – The production and 

presence in the blood and/or urine of a protein called 

a monoclonal immunoglobulin. The monoclonal 

immunoglobulin results from the transformation of a 

single B-lymphocyte or its derivative cell, the plasma 

cell. This protein is in the group of plasma proteins 

that are known as the gamma globulins. Hence, 

the term “gammopathy.” Also called M-protein or 

M-spike.

monoclonal gammopathy of undetermined 

significance (MGUS) – A benign condition in which 

there is a higher-than-normal level of a protein called 

immunoglobulin, or M-protein, in the blood. Patients 

with monoclonal gammopathy of undetermined 

significance are at an increased risk of developing 

certain types of cancer. Also called MGUS.

multiple myeloma – A type of cancer that begins 

in plasma cells (white blood cells that produce 

antibodies). 

mutation – Any change in the DNA of a cell. 

Mutations may be caused by mistakes during cell 

division, or they may be caused by exposure to DNAdamaging agents in the environment. Mutations can 

be harmful, beneficial, or have no effect. If they are 

present in cells that make eggs or sperm, they can be 

inherited; if mutations occur in other types of cells, 

they are not inherited. Certain mutations may lead to 

cancer or other diseases. 

neutropenia – A condition in which there is a lowerthan-normal number of neutrophils (a type of white 

blood cell).

pedigree – A diagram that shows relationships among 

family members. In medicine, a pedigree may also 

show the pattern of certain genes or diseases within a 

family.

phenotype – The observable physical or laboratory 

characteristics in an individual that result from the 

expression of a gene or set of genes; the clinical 

presentation of an individual with a particular genetic 

background. In WM families, WM and IgM MGUS 

are two of the most important phenotypes.

platelet – A tiny piece of a cell found in the blood 

that breaks off from a large cell found in the bone 

marrow. Platelets help wounds heal and prevent 

bleeding by forming blood clots. Also called 

thrombocyte. If the platelet count in the blood 

is lower than normal, the patient is said to have 

thrombocytopenia.

family history – A record of the relationships among 

family members along with their medical histories. 

This includes current and past illnesses. A family 

history may show a pattern of certain diseases in a 

family. Also called family medical history. When 

represented in diagram form using standardized 

symbols and terminology, it is usually referred to 

as a pedigree or a family tree.

first-degree relative – The parents, brothers, sisters, 

or children of an individual.

gammopathy – A disturbance in the production of 

immunoglobulins. Immunoglobulins are in the group 

of plasma proteins that are known as the gamma 

globulins, hence the term “gammopathy.”

gene – The functional and physical unit of heredity 

that is passed from parent to child. Genes are pieces 

of DNA, and most genes contain the information 

for making a specific protein. The proteins are 

responsible for specific characteristics or functions 

within a cell. Every gene occupies a specific location 

(or locus) on a chromosome. 

genetic disorder – Disease that is caused by an 

abnormality in an individual’s DNA. Genetic 

disorders are inherited (passed from parent to child) 

only if the abnormality is present in the germline.

genetic counseling – A communication process 

between a specially trained health professional and 

a person concerned about the genetic risk of disease. 

The person’s family and personal medical history 

may be discussed, and counseling may lead to genetic 

testing. Genetic counseling provides affected or 

at-risk individuals and families with information 

about their condition and helps them make informed 

decisions about their medical care. 

genetic marker – An alteration in DNA that may 

indicate an increased risk of developing a specific 

disease or disorder. An identifiable segment of DNA 

with enough variation between individuals that its 

inheritance along with alleles of a given gene can be 

traced; used in linkage analysis.

genetic predisposition – An inherited increase in 

the risk of developing a disease. Also called genetic 

susceptibility.

genetic screening – Analyzing DNA to look for a 

genetic alteration that may indicate an increased risk 

for developing a specific disease or disorder. Also 

called genetic testing.

genome – The complete genetic material of an 

organism.

germline – The DNA in germ cells (egg and sperm 

cells that join to form an embryo). Germline DNA is 

the source of DNA for all other cells in the body; can 

be passed from parent to child.

germline mutation – A gene change in a body’s 

reproductive cell (egg or sperm) that becomes 

incorporated into the DNA of every cell in the 

body of the offspring (child). Germline mutations 

are passed on from parents to child. Also called 

hereditary mutation. 

hyperviscosity syndrome – A clinical condition 

caused by an abnormal sluggishness of blood 

flow through peripheral vessels, caused by 

the accumulation of large proteins, such as 

immunoglobulins, in the serum; increased viscosity 

may trigger bleeding from mucous membranes, 

blurred vision, headache, dizziness, and neurological 

symptoms. 

IgM – One of the five classes of immunoglobulins; 

also known as macroglobulin. It differs from other 

immunoglobulin molecules in being five times the 

size of standard-sized immunoglobulin.

immunoglobulin – A protein that acts as an 

antibody. Immunoglobulins are made by B-cells 

and plasma cells. An immunoglobulin is a type of 

glycoprotein with two heavy chains and two light 

chains. Immunoglobulins play an essential role 

in the body’s immune system. They identify and 

attach to foreign substances, such as bacteria, and 

assist in destroying them. There are five classes of 

immunoglobulins: IgA, IgD, IgE, IgG, and IgM. 

Immunoglobulins are made up of a mixture of two 

types of protein chains. The larger of the protein 

chains is called the heavy chain and the smaller 

is called the light chain. There are two types of 

light chains, called kappa and lambda. A given 

immunoglobulin will have only one type of heavy 

chain and one type of light chain. Abbreviated as Ig. 

inherited – Transmitted through genes that have 

been passed from parents to their children.

kindred – An extended family.

leukemia – A cancer that starts in blood-forming 

tissue such as the bone marrow and causes large 

numbers of abnormal blood cells to be produced 

and enter the bloodstream.

Glossary — Words to Know (continued)

16 S

pring 2010

WaldenströmMacroglobulinemiaFamilyStudyNewsletter 17
Medical Articles

The following published articles give more detail on the 

studies described in this newsletter:

Page 2, Features of Familial WM Familial Waldenström’s 

macroglobulinemia. Seminars in Oncology, 2003, 

Volume 30, pages146-152

Page 3, Searching for WM Genes — Cytogenetics

Cytogenetics of familial Waldenstrom’s macroglobulinemia: 

in pursuit of an understanding of genetic predisposition. 

Clinical Lymphoma, 2005, Volume 5, pages 230-234

Page 4, Searching for WM Genes — Linkage study

Genetic predisposition in familial Waldenström 

macroglobulinemia: a genome-wide search of high-risk 

families provides evidence of susceptibility loci on 

chromosomes 1 and 4. American Journal of 

Human Genetics, 2006, Volume 79, pages 695-701

Page 5, Searching for WM Genes — Candidate genes Common genetic variants in candidate 

genes and risk of familial lymphoma. British Journal of Haematology, 2009, Volume 146, 

pages 418-423

Page 5, Precursor Conditions for WM Waldenström macroglobulinaemia and IgM monoclonal 

gammopathy of undetermined significance: emerging understanding of a potential precursor 

condition. British Journal of Haematology, 2007, Volume 139, pages 663-671

Page 6, Studies of WM and B-cell Cancers in the General Population Risk of lymphoproliferative 

disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström’s 

macroglobulinemia patients: a population-based study in Sweden. Blood, 2008, Volume 112, 

pages 3052-3056

Page 7, Influence of Race on Risk for WM Prevalence of monoclonal gammopathy of 

undetermined significance among adult males in Ghana. Mayo Clinic Proceedings, 2007, 

Volume 82, pages 1468-1473

Page 7, Chronic Immune Stimulation and Risk for WM Chronic immune stimulation and 

subsequent Waldenström macroglobulinemia. Archives of Internal Medicine, 2008, 

Volume 168, pages 1903-1909

Below are some other articles that we have published about WM.

1. Protein electrophoresis, immunoelectrophoresis, and immunofixation electrophoresis 

as predictors for high-risk phenotype in familial Waldenström macroglobulinemia. 

International Journal of Cancer, 2008, Volume 122, pages 1183-1188 

2. Long-term follow-up of three multiple-case Waldenström macroglobulinemia families. 

Clinical Cancer Research, 2007, Volume 13, pages 5063-5069

3. Novel aspects pertaining to the relationship of Waldenström macroglobulinemia, IgM 

monoclonal gammopathy of undetermined significance (MGUS), polyclonal gammopathy 

and hypoglobulinemia. Clinical Lymphoma and Myeloma, 2009, Volume 9, pages 19-22

4. Genetic and immune-related factors in the pathogenesis of lymphoplasmacytic 

lymphoma/Waldenström’s macroglobulinemia. Clinical Lymphoma and Myeloma, 2009, 

Volume 9, pages 23-26 

Glossary — Words to Know (continued)

The “typical” 

WM patient is 

diagnosed at 

about age 70. 

polyclonal – Descended from more than one group 

of cells, especially of genetically different origins 

(as opposed to monoclonal).

precursor condition – A condition that can lead 

to development of a particular cancer or disease. A 

precursor condition usually affects the same type 

of cells and is in the same location as the cancer 

that eventually develops. The cells in the precursor 

condition are usually atypical but are not malignant. 

A precursor condition does not necessarily develop 

into a cancer and may disappear (regress) in time. To 

develop cancer, the precursor cells must accumulate a 

series of damaging genetic changes. If these changes 

do not occur, cancer will not develop.

risk assessment – The evaluation of an individual’s 

risk of carrying a certain gene mutation, or 

developing a particular disorder, or of having a child 

with a certain disorder; this is sometimes done by 

using mathematical or statistical models including 

such factors as personal health history, family 

medical history, and ethnic background.

risk factor – Something that may increase the 

chance of developing a disease. Some examples of 

risk factors for cancer include age, a family history 

of certain cancers, use of tobacco products, certain 

eating habits, obesity, lack of exercise, exposure 

to radiation or other cancer-causing agents, and 

certain genetic changes. 

second-degree relative – An aunt, uncle, 

grandparent, grandchild, niece, nephew or halfsibling of an individual.

sporadic – A disease or condition that occurs in a 

patient who has no family history of the disease or 

condition. Also known as nonfamilial.

susceptibility gene – Inherited factor that predisposes 

a person to a certain disease or disorder. A gene 

having a germline mutation that increases an 

individual’s predisposition to a certain disease 

or disorder. When such a mutation is inherited, 

development of the illness is more likely, but 

not 100% certain. Also called a predisposing 

(disease-related) mutation.

thrombocytopenia – A condition in which there is a 

lower-than-normal number of platelets in the blood. 

It may result in easy bruising and excessive bleeding 

from wounds or bleeding in mucous membranes and 

other tissues.

unaffected – An individual who does not have 

the condition or disease that is occurring in his or 

her family.

Waldenström macroglobulinemia (WM) – An 

indolent (slow-growing) type of non-Hodgkin 

lymphoma in the bone marrow marked by increased 

levels of IgM antibodies in the blood and an 

enlarged liver, spleen, or lymph nodes. Also called 

lymphoplasmacytic lymphoma. Symptoms can be 

caused by either the lymphoma cells (for example, 

low blood counts) or the IgM (which may mistakenly 

attack normal body cells, such as platelets). When 

levels of IgM are extremely high, the blood may 

become excessively viscous (‘sluggish’ or ‘thick’), 

leading to hyperviscosity syndrome. 

white blood cell – A type of immune cell. Most 

white blood cells are made in the bone marrow and 

are found in the blood and lymph tissue. White blood 

cells help the body fight infections and other diseases. 

Granulocytes, monocytes, and lymphocytes are 

white blood cells. Also called leukocyte and WBC. 

For definitions of genetic terms that do not appear 

on this list, please refer to the online glossary 

of terms provided for patients by the NCI: http://

www.cancer.gov/cancertopics/geneticsterms-alphalist and by the National Human 

Genome Research Institute: http:// www.genome.

gov/glossary.cfm.

18 Spring 2010 Waldenström Macroglobulinemia Family Study Newsletter 19