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Press Release

Investigators at Children’s Hospital Los Angeles Discover Possible Treatment Option for Drug-Resistant Acute Lymphoblastic Leukemia

Children's Hospital Los Angeles
Posted on: 09 Apr 12

Nora Heisterkamp, PhD, and Reshmi Parameswaran, PhD, of The Saban Research Institute of Children’s Hospital Los Angeles, have found a novel approach to killing acute lymphoblastic leukemia (ALL) cells. Using a fusion toxin that specifically targets cancer cells, this novel therapeutic may offer a future alternative to patients who become resistant to chemotherapy.

“Although we have made tremendous progress in the treatment of leukemia, Dr. Heisterkamp and her colleagues’ research into drug-resistant disease fills a crucial need,” said Brent Polk, MD, director of The Saban Research Institute.

The most common cancer diagnosed in children, ALL, also accounts for 30% of adult leukemia. Although the cure rate of pediatric ALL is high, resistance to drug treatment is a major cause of disease relapse. Treatment-resistant ALL continues to be a significant medical challenge and investigators, like Drs. Heisterkamp and Parameswaran, are actively seeking alternative therapies.

Dr. Heisterkamp, who is also a professor at the Keck School of Medicine of the University of Southern California, said, “Although these are laboratory studies, we are very encouraged by our findings and we’re actively developing this approach to test in the clinic.”

Malignancies in ALL can develop from either the T-cell or B-cell lymphocytes. The majority of ALL cases are of B-cell lineage. Drs. Heisterkamp and Parameswaran had previously discovered that these leukemia cells have a protein on their surface called BAFF-R. It was known that this BAFF-R was present on mature B-cells but finding it on pre-B cells was surprising and also presented a therapeutic target for selectively killing the pre-B ALL cells.

The investigators made use of the fact that a protein called BAFF specifically binds to the BAFF-R protein and then is allowed entry into the cell. They tested a toxin-BAFF fusion protein. Using a “Trojan horse” approach, the investigators showed that when ALL cells were exposed to the BAFF-toxin, the ALL cells bound the BAFF-toxin, transported it inside the cell, and were then killed. The BAFF-R is only present on certain blood-forming cells, so the BAFF-toxin is not expected to harm any other cells, making it much less toxic than standard chemotherapy.

Results of the study were published in the February 29 issue of Leukemia. Collaborators on the study include M. Yu, M. Lim, and J. Groffen, all of The Saban Research Institute, as well as Michael G. Rosenblum and M-A Lyu, of the MD Anderson Cancer Center.

About Children’s Hospital Los Angeles

Children's Hospital Los Angeles has been named the best children’s hospital in California and among the best in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States, is one of America's premier teaching hospitals and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.

For more information, visit www.CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog: www.WeAreChildrens.org.

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Last updated on: 09/04/2012

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