Inhibiting one gene -- even
temporarily -- can improve cure rates for blood cancer patients who receive
stem cell transplants. This strategy may also help patients with genetic
and autoimmune diseases who are also treated with stem cell transplants.
Researchers at H. Lee Moffitt Comprehensive Cancer Center in Tampa, led
by William Kerr Ph.D., and funded by The Leukemia & Lymphoma Society, have
discovered that the SHIP gene plays a critical role in graft vs. host
disease (GvHD), in which a donor's immune cells (the "graft") attack a stem
cell transplant patient's healthy tissue (the "host") as well as cancer
cells. By using genetically engineered mice, the researchers have shown
that inactivating the SHIP gene for just one week protects transplant
recipients from acute GvHD. This protection is seen even when the graft
contains extra immune cells to help the graft "take" or when the graft
cells are completely mismatched to the recipient. The findings will be
published in the March 1st issue of the "Journal of Immunology."
Allogeneic transplants are the best curative option for many blood
cancer patients because the donor's cells replace critical blood cells lost
during a patient's pre-transplant chemotherapy, and because the donor's
cells can help kill any remaining cancer cells to prevent relapse. But,
poorly matched donor grafts can be rejected, just as in organ transplants,
or cause GvHD. "Currently, suitable donors can only be found for 20 to 30
percent of patients who might be cured by allogeneic transplants," said
Kerr. "But by learning which genes control graft rejection and GVHD, new
targeted treatments might be used to make transplants successful and safe
for more patients."
Since the SHIP gene is also present in humans, Dr. Kerr says the team's
findings are important for cancer patients. Kerr said that with adequate
funding, clinical trails using SHIP-targeting strategies in human patients
could only be a few years away.
"If we can identify approaches to inhibit SHIP in patients, then we
could potentially reduce the risk of GVHD in matched transplants that are
currently used to treat blood cancer patients, perform allogeneic
transplants even when a matched donor cannot be found, and increase the
number of donor immune cells that can be given to patients post-transplant
to combat cancer relapse," Kerr said.
SHIP inhibitor drugs are already being developed and Dr. Kerr has shown
that a genetic treatment strategy called RNA interference (RNAi) can also
be used to turn the SHIP gene off. Other scientists have shown that RNAi
can be used to turn-off specific genes in mice and non-human primates.
Kerr is a recipient of the Society's Scholar Award -- a program that
provides funding to highly qualified investigators conducting original
research on leukemia, lymphoma or myeloma.
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society(R), headquartered in White Plains, NY,
with 66 chapters in the United States and Canada, is the world's largest
voluntary health organization dedicated to funding blood cancer research
and providing education and patient services. The Society's mission: Cure
leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality
of life of patients and their families. Since its founding in 1949, the
Society has invested more than $486 million in research specifically
targeting leukemia, lymphoma and myeloma. Last year alone, the Society made
4.2 million contacts with patients, caregivers and healthcare
professionals.
For more information about blood cancer, visit LLS or call the
Society's Information Resource Center (IRC), a call center staffed by
master's level social workers, nurses and health educators who provide
information, support and resources to patients and their families and
caregivers.
The Leukemia & Lymphoma Society
LLS