Message from the Founders

S P R I N G
2 0 1 5
inSights
A Quarterly Newsletter from Beat Leukemia With Connor
Issue No. 2
Beat Leukemia With Connor is a
charitable entity set up with the
following main mission:
Message from the Founders
Dear Friends and Supporters
Now in our seventh month of fundraising, we continue to
maintain tremendous momentum, surpassing USD150,000 in
funds raised for pediatric leukemia research. We are humbled
by your generosity and support.
In this issue, we share with you an arts-in-medicine program
that uses a simple string of beads to define the courage and
resilience of children undergoing cancer treatment. You will
also find an update on one of the research projects you are
supporting through BLWC.
Please help us build awareness of the need for funds for
childhood leukemia research by sharing this newsletter with
your friends and visiting our website. As always, we look
forward to hearing from you.
With Warmest Regards
Conwell Tam & Douglas Beal

To improve cure rates for
childhood leukemia by funding
research that focuses on
understanding the origins of the
disease using the most advanced
medical technology available

To fund research on
understanding and treating
resistant disease, and on
developing targeted treatment
therapies for childhood leukemia
Proceeds go entirely towards
childhood leukemia research. No
administrative charges are deducted so
every cent of your donation will
contribute to finding more effective
cures for childhood leukemia.
To learn more about Connor’s story
and the work we do, please visit:
www.beat-leukemia-with-connor.com
inSIGHTS
SPRING 2015
Research Focus
Researchers working on a project sponsored by Beat Leukemia With Connor have
identified a cytokine receptor that, in mutated form, leads to hyper-proliferation of
myeloid cells, taking us one step closer to understanding how leukemia may happen
Leukemia is a group of cancers that usually
begins in the bone marrow and results in a high
number of abnormal white blood cells. These
white blood cells are immature, do not function
normally and are called blasts or leukemic cells.
The exact cause of leukemia is unknown.
Without understanding the mechanism through
which healthy bone marrow transforms into one
which produces leukemic cells, it is difficult to
design a treatment protocol that maximizes the
cure rate for this disease.
What is Leukemia?
Clinically and pathologically, leukemia is
subdivided into a variety of large groups. The
first division is between acute and chronic
forms. Acute leukemia is characterized by
rapid increase in leukemic blasts. Immediate
treatment is required due to rapid progression of
the disease. Most childhood leukemia is acute.
Chronic leukemia is characterized by slow
build-up of blasts. It may take months or years
to progress and is more common in older
individuals.
Leukemia is further subdivided according to
which types of blood cells are affected:
Lymphoblastic leukemia – the cancerous
change takes place in the type of marrow cell
that goes on to form lymphocytes, infectionfighting immune system cells.
Myeloid leukemia – the cancerous change takes
place in the type of marrow cell that forms red
blood cells, some types of white cells and
platelets.
Acute Myeloid Leukemia is further sub-divided
into 7 types of leukemia. It is this heterogeneity
of disease that makes it difficult to treat, with a
lower cure rate than other leukemias. Connor
suffered from Acute Megakaryoblastic
Leukemia (AMKL) – the form associated with
the marrow cells that produce platelets.
Individuals with Down Syndrome (DS) carry
increased risk of developing leukemia, and the
form they suffer from are classified as DSAMKL.
Researchers know that DS-AMKL is associated
with a mutation in a protein called GATA1.
GATA1 plays a role in red blood cell
development by regulating the switch from fetal
hemoglobin to adult hemoglobin. Mutations in
the GATA1 gene have been linked to several
diseases, including DS-AMKL.
From Transient Leukemia to DS-AMKL
Another form of leukemia also unique to
individuals with DS is Transient Leukemia
(TL). TL is of fetal origin (acquired from birth)
and is characterized by GATA1 mutation.
Most cases of TL resolve spontaneously without
treatment, however 20-30% of children with TL
go on to develop DS-AMKL within the first 4
years of life. The factors or additional
mutations that underlie this progression remain
elusive. One of the projects that Beat Leukemia
with Connor sponsors aims to identify the
mutations in this progression from TL to overt
AMKL.
Research . Hope . Cure
inSIGHTS
SPRING 2015
This project, led by Dr. Jan-Henning Klusmann
of the Hannover Medical School, uses Next
Generation Sequencing (NGS) to identify
additional mutations in DS-AMKL.
Thereafter, researchers characterize the
biological impact of the mutation in functional
studies to understand the pathogenesis of the
disease and to develop targeted and less toxic
therapeutic approaches to DS-AMKL. The
ultimate goal of the project is to identify ways to
prevent progression from TL to DS-AMKL.
The project also has broader implications for
other forms of leukemia. It is conceivable that
if researchers can understand the mechanism
through which one type of leukemia can remain
latent over a period of time and then present as
another type, the exact causes of leukemia can
be identified and in the future, certain types of
leukemia maybe preventable.
Project Update
Researchers have now successfully completed
the functional in-vitro (i.e. in the petri dish)
evaluation of one gene that is found to mutate
in DS-AMKL. This gene is a cytokine receptor,
a protein that controls proliferation of myeloid
cells. In healthy marrow, the activity of such
receptors is controlled by three different
cytokines. However, our researchers have
found that a mutation in this gene causes the
cytokine receptor to act independently, without
the presence of cytokines. This leads to the
growth of cells in the absence of cytokines.
Additional tests done by the research team on
hematopoietic stem cells conclude that the
mutated form of the cytokine receptor leads to a
hyper-proliferation of myeloid cells.
Researchers will conduct in-vivo (mouse
transplantation) studies in the next stage of the
project.
Additional Research Update
Researchers have concurrently completed
analysis of data collected from an 8-year
worldwide study on AMKL. An interesting
observation was that several patients without
any feature of DS had Trisomy 21 as well as
GATA1 mutation in their blasts. Some had
Trisomy 21 mosaicism in a fraction of their
cells, while others acquired Trisomy 21 only in
the AMKL blasts. These observations will be
used to plan a follow-up study.
Dr. Med. Jan-Henning Klusmann
Dr.Klusmann is Fellow of Pediatric Hematology and Oncology at
the Hannover Medical School. He heads up the Emmy Noether
Junior Research Group, which aims to understand the molecular
basis for the development of myeloid leukemia (AML) using stateof-the-art molecular techniques. The focus of the group’s research is
children with Down Syndrome, who are highly predisposed to
develop AML. Dr. Klusmann has been awarded a number of
professional distinctions, including the ASH Outstanding Abstract
Achievement Awards and the Leukemia Clinical Research Awards
2011 by the German Society of Hematology and Oncology.
To contact Dr. Klusmann, please email [email protected]
Research . Hope . Cure
inSIGHTS
SPRING 2015
Courage and Resilience on a String
When Connor began leukemia treatment in Germany, we met children in the pediatric oncology ward with
long colorful strings of beads hanging on their IV stands. We did not know what the beads represented but
little did we realize Connor would soon have his own string of beads and that after his death, his “beads of
courage” would become a remembrance of his life, courage and resilience.
What are these beads?
The concept of “beads of courage” originated in the
United States and was developed and piloted by Jean
Baruch at Phoenix Children’s Hospital in February
2003. The key premise of the initiative was, through
arts-in-medicine, to support and strengthen children
and families coping with cancer. Through the
program, children tell their individual stories using
colorful beads as meaningful symbols of courage that
they receive to honor and acknowledge each step of
their treatment journey.
Since 2003, the program has reached globally, serving as inspiration for similar resilience-based
intervention in children’s hospitals around the world. Whilst the beads may be glass or rubber,
and carry different names across the world (for example, “Mutperlen” in Germany,
“KanjerKetting” in the Netherlands, “Rainbow Trail” in Scotland, “Beads of Courage” in the US
and Canada), all programs serve the same fundamental purpose: to support children fighting
cancer, and to help children find meaning in illness.
How does it work?
A child diagnosed with cancer gets, at admission
to the hospital, a wax rope, a bead with an anchor
(a sign of hope) and alphabet beads that form the
child’s name. Depending on the therapies and
treatments, a variety of beads will follow in the
next few months or years.
Each bead symbolizes an engagement, a
milestone, a treatment, a particularly good or bad
day. There are small red beads for every blood
draw, a small purple and white ball for every bone
marrow aspirate. The Chemo-Kasper bead is
awarded at the start of every chemotherapy block
and a bead in the shape of a hat is awarded for hair
loss. There are more than 40 types of beads
covering a wide range of treatment milestones:





Logistics: admission to the hospital or to the ICU, being in isolation etc.
Diagnostics: lumbar punctures, scans, bone marrow aspirates etc.
Treatment: chemotherapy, radiotherapy, stem cell transplant etc.
Supportive treatment: blood transfusions, nebulizers, nasogastric tubes etc.
Other events: birthdays, hair loss, a good day, a bad day etc.
Research . Hope . Cure
inSIGHTS
SPRING 2015
The string of beads grows longer, becoming a “rainbow trail” that
represents the personal story of the child. Recognizing that some children
may die despite treatment, there is a bead that marks the end of life
What do the beads achieve?
Healthy children have concrete ways
to measure achievements in school or
on the soccer field. Children fighting
cancer frequently spend months or
years struggling with how to define
the monumental milestones they
achieve and the exceptional bravery
they show.
The string of beads achieves the purpose of telling each child’s story and is a unique personal diary
for the duration of the treatment. Treatments and interventions translate into achievements and
concrete proof of the fight against cancer. They give children colorful moments in the cancer ward,
help them to stay strong and motivated throughout treatment and deal with disease in a positive
way. The beads provide an opportunity for children to talk to other patients in the cancer ward, and
are used to explain to family members what happened during treatment. Most importantly, the
children are proud of their “beads of courage” – they know the meaning of each bead and exactly
what each stands for.
VOKK & KanjerKetting
The beads program KanjerKetting, as we knew it in Germany, was developed by Vereniging
Ouders, Kinderen & Kanker (VOKK or “The Dutch Childhood Cancer Parent Organization”)
after in-depth research on the effectiveness of the beads in a pediatric oncology setting. Today,
KanjerKetting is adopted by many children’s hospitals across Europe. Beads are given to
hospitals free of charge. Children and families also receive the beads free of charge. To learn more
about VOKK and KanjerKetting, please visit www.vokk.nl and www.kanjerketting.nl
Connor’s Beads of Courage
Today, 9 months after Connor’s death, we continue to treasure
his beads of courage. We remember the moments we threaded
the beads together, we remember the delight on his face when he
was awarded a colorful bead for completing yet another session
of radiotherapy or despite the tears and pain of his seventh
lumbar puncture. The beads are a concrete reminder of his
courage and resilience, an immense source of pride for his
achievements despite the fight he lost. We are thankful that
organizations such as VOKK continue to promote programs like
KanjerKetting, and hope that children’s hospitals around the
world continue to bring this initiative to families and children
suffering from cancer.
Research . Hope . Cure