University
of Florida researchers have successfully used
molecular probes to detect subtle differences in
leukemia cells from patient samples, an achievement
that could lead to more effective ways to diagnose and
treat cancer.
The strategy, described in a recent issue of
Clinical Chemistry, involves engineering short, single
strands of DNA or RNA called aptamers to seek out and
bind with specific proteins in body fluids.
UF scientists designed the aptamers to bind to
cells and molecules associated with leukemia, a cancer
of the blood and bone marrow that annually claims
about 21,000 lives in the United States, according to
the National Cancer Institute.
Researchers also found the first evidence that
slight molecular differences can exist even within the
same samples from patients with adult T-cell leukemia,
a cancer that strikes the immune system’s own
protective cells.
“Our selective aptamers clearly confirm there are
several subcategories of adult T-cell leukemia,” said
Weihong Tan, a UF Research Foundation professor of
chemistry at the College of Liberal Arts & Sciences
and a member of the UF Shands Cancer Center. “At
present, doctors have had only their experience to
rely upon to determine the best treatment for these
patients. Our findings will give doctors an effective
tool to more precisely make a diagnosis and to tailor
treatments.”
UF researchers built designer probes using cancer
cells as a template, capitalizing on the ability of
aptamers to fold into well-defined, three-dimensional
structures that bind to targets. The process relies on
the fact that different types of cells exhibit unique
surface features, so aptamers can recognize and bind
with these target cells — and only these cells — even
in the presence of other, closely related cells.
The scientists found that three of six aptamers
they selected for study adhered to all types of
cancerous cells but ignored normal blood and bone
marrow cells. In combination, the six aptamers
produced distinct patterns that characterize different
cancer cells, suggesting that the technique could be
useful to detect the molecular fingerprints of cancer
in people.
The next step toward developing a clinical
diagnostic tool involves matching patient data with
these molecular profiles. The research team — working
with Dr. W. Stratford May, director of the UF Shands
Cancer Center, and Dr. Ying Li, a clinical assistant
professor of pathology, immunology and laboratory
medicine in the College of Medicine — has analyzed
additional patient samples to build a database that
may one day help doctors select the best treatment
strategies.
“We are linking the medical histories of patients
to specific aptamer binding patterns,” said Tan, who
is also affiliated with the UF Genetics Institute. “We
should soon be able to say patients who belong to this
specific molecular binding pattern should have
‘such-and-such’ treatment. Different molecular
patterns of cancer patients will point to different
treatments.”
Current tests to diagnose leukemia use antibodies,
proteins that have the ability to identify harmful
substances. But such methods do not capture subtle
variances in the molecular signature of cancer cells.
Once an aptamer probe has proved its utility, it
can be inexpensively reproduced in a DNA synthesizer.
“Physical scientists mostly use cultured cellular
models to demonstrate a principal, and then we leave
the findings behind for the biological scientists to
use — if they want,” Tan said. “But through
collaboration we have pushed the demonstration through
to an almost clinical application.
