Visit our website: www.ChildrensHospitalLA.orgResearchers at Childrens Hospital Los Angeles May Have Discovered an Explanation for the Increased Relapse Rate of Leukemia in Obese Children and Adults

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                      Marlen Bugarin at (323) 361-5567

EMBARGOED UNTIL:  1:00 PM (ET) September 22, 2009

LOS ANGELES – An article to be published in the September 22, 2009, issue of the journal Cancer Research highlights the role of the fat cell in fostering leukemia chemotherapy resistance, and, according to the senior author, Steven D. Mittelman, M.D., Ph.D., “…may help explain the increased leukemia relapse rate in obese children and adults.”

Dr. Mittelman is fellowship research director in the Division of Endocrinology and Metabolism at Childrens Hospital Los Angeles, and assistant professor of pediatrics, physiology and biophysics at the Keck School of Medicine of the University of Southern California.

The article entitled, “Adipocytes Impair Leukemia Treatment in Mice,” was inspired by a previous study led by a colleague, Anna Butturini, M.D., in the Division of Hematology-Oncology at Childrens Hospital, which found that obese children diagnosed with leukemia have a 50-percent higher chance of relapsing than lean children.

To investigate the causes, Dr. Mittelman worked with Nora Heisterkamp, Ph.D., also in the Division of Hematology-Oncology at Childrens Hospital and an expert in leukemia cell biology.

“We found that some leukemia cells were ‘hiding out’ in the fat tissue during chemotherapy,” Dr. Mittelman said.  “To figure out whether the fat cells were allowing the leukemia to avoid the chemotherapy, we cultured fat and leukemia cells together.  When we treated the leukemia cells with the many traditional chemotherapy drugs used in children with leukemia, they each worked less effectively when the leukemia cells had fat cells nearby.” 

 “The fat cells seem to produce survival signals for the leukemia cells,” said first author James Behan, a medical student at USC’s Keck School of Medicine, “…which prevent the leukemia cells from entering apoptosis, or programmed cell death.”

Dr. Mittelman and his colleagues at The Saban Research Institute of Childrens Hospital Los Angeles and USC’s Keck School of Medicine concluded that the fat cells somehow protect leukemia cells from chemotherapy.  And since obese children have more, larger fat cells than thin kids, that might be the reason for the poorer prognosis seen in obese patients.

Dr. Mittelman added, “Leukemia is the most common cancer in children, so it is important that we understand what causes some children to relapse.  Also, given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment.”

David Hockenbery, M.D., member of the Fred Hutchinson Cancer Research Center and professor or internal medicine at the University of Washington, said, “This study provides striking experimental support for the clinical observations that obesity is associated with poor prognosis in multiple cancer.

“In addition, by highlighting a potential communication between adipocyte and leukemia cells, this research will stimulate efforts to find a diffusible factor that protects leukemia cells from chemotherapy,” Dr. Hockenbery said.

The research was supported by grants from the National Institutes of Health and the National Cancer Institute’s Centers for Transdisciplinary Research on Energetics and Cancer.

Dr. Mittelman received a bachelor’s degree from the University of California, Los Angeles (1993) and a combined medical degree and doctorate from the Keck School of Medicine of the University of Southern California (2001).

He completed an internship (2001-02) and residency (2002-04) at Childrens Hospital Los Angeles.  He also completed a fellowship in pediatric endocrinology from Childrens Hospital Los Angeles (2004-06).

Dr. Mittelman’s major areas of research interest include the association between obesity at diagnosis and increased risk of acute lymphoblastic leukemia relapse in children, and hormonal control of appetite in adolescent obesity.

Founded in 1901, Childrens Hospital Los Angeles has been treating the most seriously ill and injured children in Los Angeles for more than a century, and it is acknowledged throughout the United States and around the world for its leadership in pediatric and adolescent health. Childrens Hospital is one of America’s premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California since 1932.  It is a national leader in pediatric research.

Investigators at The Saban Research Institute of Childrens Hospital Los Angeles are working to create a world in which all children are healthy – a world in which they are no longer threatened by such diseases as cancer, congenital heart defects, diabetes, sickle cell anemia, epilepsy, immune deficiencies and respiratory disorders.  They ask basic questions about human biology, find new ways to see inside the body, explore genetic mysteries, develop promising drug treatments and test preventive strategies – scientific inquiries that benefit both children and adults. The Saban Research Institute is among the largest and most productive pediatric research facilities in the United States, with 91 investigators at work on 232 laboratory studies, clinical trials and community-based research and health services.  It is one of the few freestanding research centers in the nation to combine scientific laboratory inquiry with patient clinical care – dedicated exclusively to children - and its base of knowledge is widely considered to be among the best in pediatric medicine.

Since 1990, U.S. News & World Report and its panel of board-certified pediatricians have named Childrens Hospital Los Angeles one of the top pediatric facilities in the nation.  Childrens Hospital Los Angeles is one of only 10 children’s hospitals in the nation – and the only children’s hospital on the West Coast – ranked in all 10 pediatric specialties in the U.S. News & World Report rankings and named to the magazine’s “Honor Roll” of children’s hospitals.

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