Children's Hospital researcher leads multipronged attack on infant leukemia

New grant supports targeted treatments for stubborn disease

While survival rates for childhood leukemia have dramatically improved over the past 30 years, infants with this blood cancer continue to face difficult odds. Infant leukemia resists treatments such as chemotherapy and stem cell transplants that may be effective in older children, and infants are especially vulnerable to treatment side effects.

A new research effort led by a leukemia expert at The Children's Hospital of Philadelphia seeks to harness in-depth understanding of genes and molecular pathways to develop highly specific drugs designed to kill leukemia cells while causing few or no toxic effects on normal cells.

A five-year, $6.25 million Specialized Center of Research (SCOR) grant from the Leukemia & Lymphoma Society brings together a diverse study team of researchers from leading medical centers to develop innovative treatments for infant leukemia. "Our goal is to streamline advances in molecular medicine to find new treatment options," said Carolyn A. Felix, M.D., principal investigator of the SCOR grant. A pediatric oncologist at The Children's Hospital of Philadelphia, Dr. Felix also is a professor of Pediatrics at the University of Pennsylvania School of Medicine.

The society recently announced its grant award in targeted therapies for infant leukemia from its national office in White Plains, N.Y. The SCOR grant draws on research collaborators from a variety of disciplines to discover new approaches to treatment.

In addition to researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania, the grant includes collaborators from the University of New Mexico, Johns Hopkins University, Stanford University and Tulane University.

Especially integral to this effort to advance new treatments from bench to bedside, the investigators also will work closely with the Children's Oncology Group, the cooperative clinical research organization of pediatric cancer centers throughout North America. "Even the largest medical center has a relatively small number of patients with infant leukemia," said Dr. Felix. "Collaborating with the Children's Oncology Group allows us to capture data about and treat the vast majority of infants throughout North America who have acute leukemia."

The full grant encompasses four projects, each of which hones in on a piece of the infant leukemia puzzle. In infant leukemia, a gene called mixed lineage leukemia (MLL) breaks and recombines with one of many partner genes to form a translocation, an abnormal rearrangement within a chromosome. Because MLL plays a critical role in blood cell development, the translocation causes the overproduction of defective white blood cells that are the hallmark of leukemia.

Dr. Felix has pioneered methods to identify and describe the features of MLL translocations. Her project within the SCOR grant will investigate how potential drugs may trigger programmed cell death, called apoptosis, in leukemia cells in infants. Another project, led by Cheryl L. Willman, M.D., of the University of New Mexico, will use microarrays (DNA chips) to identify drugs that may selectively attack cells with MLL translocations. The project also seeks to unravel the molecular circuitry in leukemia cells in order to predict those infants most likely to benefit from specific targeted drugs.

Donald Small, M.D., Ph.D., of Johns Hopkins University, leads a SCOR project to advance the development of new drugs to target abnormalities in a gene called FLT3 that are associated with uncontrolled growth of the leukemia cell population.

A final team under the SCOR grant, led by Michael Cleary, M.D., of Stanford University, will characterize the MLL leukemia stem cell that gives rise to all other leukemia cells, because the stem cells are essential targets for new treatment to eradicate the disease. Core research facilities at several other academic medical centers will provide specialized support in analyzing data.

The SCOR officially began on October 1. "This grant from the Leukemia and Lymphoma Society creates a unique opportunity to produce advances against a very challenging form of leukemia," said Dr. Felix. "The SCOR grant brings together researchers from around the United States and harnesses our efforts to build bridges between basic science and bedside treatments and have the utmost impact for infants with this dread disease."


About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit

Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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