Scientists and detectives share a lot in common.
Both seek answers to unresolved questions and both combine a systematic approach with intuition. Both also are known as investigators.
|David Senitzer (Photo by p.cunningham)|
In the case of City of Hope’s Histocompatibility Laboratory, the results of its investigations have high stakes. The work of the laboratory is vital to the outcome of transplants using donated bone marrow and stem cells. Its contributions helped make possible City of Hope’s recent milestone 10,000th hematopoietic cell transplant — and transplants worldwide.
Patients undergo hematopoietic cell transplantation for serious blood-based diseases like leukemia. The procedure reboots a patient’s circulatory and immune system using healthy cells from the patient or a donor.
It all begins with human leukocyte antigens (HLA). The combination of these proteins, which are found on the surface of cells, acts as an identification tag that keeps the immune system from turning against the body’s own cells. Everyone has their own HLA combination; scientists estimate between 10,000 and 13,700 combinations are possible.
Most importantly, a close HLA match between patient and donor is essential to a successful transplant. So when a patient needs a transplant using donated cells, the Histocompatibility Laboratory searches diligently for the closest match using high-resolution techniques to screen tissue samples from potential donors. The lab plays the role of matchmaker in the search for a compatible donor.
The Histocompatibility Laboratory also helps monitor the success of transplantation following the procedure — an area where the team has innovated significantly.
One of the potential risks after transplantation is graft-versus-host disease, in which the donor’s immune system identifies the patient’s tissue as foreign and attacks it. A patient’s body also may reject donated cells.
When some of the patient’s original blood cells return after transplantation, it increases the threat that disease will recur or signals that the patient’s body is rejecting the graft — presenting an important warning sign. To stay ahead of this danger, physicians test for what they call chimerism: a patient’s hybrid status as one person harboring another person’s blood and immune system.
“If we detect the patient’s cells, physicians will alter the way they treat the patient,” said David Senitzer, Ph.D., director of the Histocompatibility Laboratory. “The earlier you catch these problems, the easier they are to deal with.”
To help, HLA researchers adapted methods used by their fellow investigators in police work.
Standard blood tests for chimerism used to take up to six weeks to return results — making them unhelpful as an early warning sign. In 2004, Senitzer and his colleagues struck upon an idea to speed the process: Use tools from the crime lab.
Police forensic investigators use an analytic method called short tandem repeat to compare an individual’s unique DNA to evidence found at a crime scene. The test also is widely used to confirm or deny paternity. And it only requires 24-hour turnaround.
“We were one of the first labs in the country to develop the short tandem repeat method for determining chimerism,” said Senitzer. “In the early days, I did a lot of traveling to teach it. Since then, it has been adopted by laboratories all over the country and Europe.”
Within the last year or so, the Histocompatibility Laboratory has adopted a test for chimerism that is more sensitive still, by a factor of 100 — and team members vow to keep up their investigations.
To learn more about the lab and how HLA techniques work, visit www.cityofhope.org/hla.