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Obesity hinders chemotherapy treatment in children with leukemia

Submitted by on 25 October, 2018 – 4:32 am
Obesity is a major factor contributing to resistance to chemotherapy and increased relapse rates among children with leukemia, according to recent studies, first published online in Cancer Research, a journal of the American Association for Cancer Research.

Obesity is associated with increased incidence and mortality of many cancers. Leukemia is the most common cancer in children, affecting more than 2,000 children each year in the United States, according to background material in the study.

Given the increasing prevalence of obesity worldwide, these findings could have important implications for the treatment of cancer and may help explain the higher relapse rate of leukemia in obese patients, said lead study investigator Steven D. Mittelman, MD, Ph.D. Mittelman, is the research director of communion with the Division of Endocrinology, Childrens Hospital Los Angeles, assistant professor of pediatrics, physiology and biophysics at the Keck School of Medicine, University of Southern California.

“Obesity may increase cancer incidence and mortality through a variety of ways. It can affect the immune system’s ability to stop cancer, or predispose cells to become cancerous,” Mittelman, he suggested. “Once you have cancer, and if you are obese, fat cells can impair the ability of chemotherapy to fight cancer cells.”

This study was inspired by an earlier study by a colleague, Anna Butturini, MD, associate professor of clinical pediatrics in the Division of Hematology / Oncology at Children’s Hospital, which showed that obese children diagnosed with leukemia have a 50 per cent more relapses compared with children to read.

Use of preclinical models, Mittelman and colleagues investigated the reason why obese children were at greater risk of relapse. They developed a mouse model of obesity and leukemia, and leukemia cultured fat cells together, and leukemia cells treated with traditional chemotherapy drugs used in children – nilotinib vincristine, daunorubicin and dexamethasone.

Obese mice with leukemia had higher rates of relapse than lean mice after treatment with first-line drug vincristine chemotherapy. Chemotherapy treatments all worked less effectively in the culture when fat cells were near. When the mice relapse of leukemia, researchers found leukemia “hidden” in the fatty tissue during chemotherapy, according to Mittelman.

“These leukemia cells attack of four drugs in different ways, so when we saw the fat cells by blocking we realized it could be an important mechanism to promote their ability to live and divide,” he said. “We were surprised to find leukemia cells in fat tissue.

David Hockenbery, MD, of Fred Hutchinson Cancer Research Center and professor of internal medicine at the University of Washington, said: “This study provides experimental support for striking clinical observation that obesity is associated with poor prognosis in multiple cancers.

The researchers demonstrated that the co-culture of leukemia cells with adipocytes decreases the response to multiple chemotherapeutic agents. Therefore, adipose tissue may function as a “safe haven” for the leukemia cells during treatment, according to Hockenbery. Based on the finding that adipocytes accumulate chemotherapeutic drugs, advised him to pay careful attention to dose adjustments based on pharmacokinetic measurements.

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

More research is needed to determine how fat cells are part of the tumor microenvironment and how to block potentially lifesaving treatments, according to Mittelman. Researchers are conducting additional studies to evaluate other chemotherapy drugs such as obesity may or may not affect the treatment and the effect of fat cells found in bone marrow in leukemia.

Source: American Association for Cancer Research (web)

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