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ASIAN INNOVATION AWARDS: THE WINNERS 2003: GOLD
AWARD
Kids' Cancer Heroes
A Singapore team has invented a simple test for
childhood leukaemia that promises safer treatments and higher
cure rates for kids in the developing world
By Trish Saywell/SINGAPORE
Issue cover-dated
November 06, 2003
MALAYSIA-BORN ALLEN YEOH
was so keen on medicine that his mother sent him to live
with his godparents in Singapore so he would have a better
chance of entering medical school there. He was just 14 years
old. "She was so worried that I would go crazy not doing
medicine," recalls Yeoh, now a paediatric oncologist and
assistant professor at the National University of Singapore.
That goes for his colleague Limsoon Wong, too. The head of
research at Singapore's Institute for Infocomm Research, who
holds a doctorate in computer science, was dispatched from
Malaysia to Singapore at the same age to enhance his chances
of getting into a good university. For the thousands of
children suffering from leukaemia in Asia, it's a good thing
their parents didn't take any chances.
Yeoh and Wong teamed up to design a revolutionary gene
chip-based analysis system that enables doctors to diagnose
and better treat acute lymphoblastic leukaemia, the most
common type of childhood cancer. Members of their research
team include computer scientists Jinyan Li and Huiqing Liu of
the Institute for Infocomm Research. The breakthrough won them
the Gold Award in the REVIEW's Asian Innovation Awards.
The beauty of their discovery is that it will help doctors
refine therapies for the disease by identifying and
stratifying the risk profiles of each patient in one simple
test. "We have over the last 30 years in Singapore been able
to go from curing less than 5% to about 75% of cases of this
type of leukaemia," Yeoh explains. "But relapse remains a
problem."
Though the diseased leukaemia cells look identical under
the microscope, there are at least six different subtypes of
childhood acute lymphoblastic leukemia, or ALL, that usually
have different clinical behaviour and need different
therapies. To avoid undertreatment--which causes a relapse and
eventually death--or overtreatment--which causes severe
long-term side effects from radiation and chemotherapy--it's
important to quickly and accurately diagnose the subgroup.
Currently, identifying the various subtypes is an
imprecise, expensive process that requires expertise in four
different and highly skill-dependent types of laboratory
tests. These tests are only available in developed countries,
not in hospitals in the developing world.
As a result, children outside the United States and Europe
are typically given a standard treatment for the disease that
overtreats low-risk patients and undertreats those who have a
high risk of relapse. "I wondered if we could have a single
test to tell us the same story as all these other tests do and
then simplify it and apply it to the developing world," Yeoh
says, adding that about 80% of ALL cases are found in the
developing world.
Leukaemia is a genetic disease: A mutated gene in the
cell's nucleus sends out messages to the cell to make it
divide uncontrollably. The gene chip measures the level of
various messages that come out from the nucleus of the
leukaemia cell. By analyzing the profiles of the different
messages in different types of leukaemia, it allows doctors to
identify a leukaemia variant based on its message profiles
alone.
Yeoh worked on the project at St. Jude Children's Research
Hospital, a charity hospital in Memphis, Tennessee. He tapped
the strength and synergy between clinicians and scientists
from St. Jude's, the National University Hospital and the
Institute for Infocomm Research. The hospital provided a
decade's worth of samples and $1 million for his research.
Wong and his team at the Institute for Infocomm Research
then mined Yeoh's data. The results were ready in about two
months. "I'm a mathematician and data mining is quite closely
associated with mathematics--how to deduce patterns, how to
know whether those patterns have sufficient statistical
strengths," explains Wong. The discovery by Yeoh and his team
will lead to a single, simple and much cheaper way of
diagnosing and risk-profiling children. Indeed, his gene
chip-based analysis can distinguish high-risk patients who
have up to an 80% risk of relapse and low-risk patients with
just a 3% risk of relapse.
Another benefit of the test is that kids with less risk of
a relapse will not be overtreated with chemotherapy, which has
serious side effects including reducing a patient's
intelligence level and hormonal changes. "I could see these
kids become slower and I could see the frustration of their
parents," Yeoh says. "It's very sad. I have a kid that I saw
in clinic whose brain had been radiated and [his] mom says,
'He's done well with language but has done poorly at maths and
abstracts' . . . The drop in IQ is 10 points. That's not
acceptable in Singapore."
What's more, the risk of a second leukaemia-related or
treatment-related cancer is significantly higher in children
who receive radiation therapy of the brain and spine, Yeoh
says. He points out that there's a 2.7% chance of the
development of a second cancer if a child does not receive
radiation treatment but the number jumps to 23% if a child
receives the treatment. In a recent study published in The New
England Journal of Medicine, researchers found that the risk
of a second cancer was significantly higher in the 597
patients who received radiation therapy than in the 259
patients who did not receive radiation therapy.
That's why the team's gene chip will be so critical in the
future treatment of the disease. Yeoh's next project is to use
the gene-chip technology to interpret and look into ways to
disrupt messages that a leukaemia cell's deranged nucleus is
sending out to cause it to become cancerous. If he can do
that, he says, he'll be a very happy man. "That's the
excitement of research," he says, "to constantly try to
improve."
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