The most common type of childhood cancer is known as acute lymphoblastic leukemia (ALL). Approximately 2,400 children and adolescents under the age of 20 are diagnosed with ALL every year in the United States, according to the National Institutes of Health, most of whom will survive the disease.

ALL is a cancer of the white blood cells, which are the cells in the body that normally fight infection. With current treatments, more than 95 percent of these children attain remission and an average of 80 percent become cancer free at least 5 years from diagnosis. However, some children do not respond to treatment and many patients differ greatly in their responses to their treatments. According to researchers from St. Jude Children’s Research Hospital, genetic variations play a role in how children will respond to ALL therapy.

The researchers have identified more than 100 inherited genetic variations that affect a child’s response to ALL treatment that might lead to the development of better therapies. The findings of this new study were published in the Journal of the American Medical Association.

According to Mary Relling, Pharm.D. of St. Jude Children’s Research Hospital and a member of the research team, “This study differs from most previous investigations of gene variations linked to chemotherapy outcome because those studies focused only on the genes of the leukemic cells themselves.” She explained that the new study “focused on genomic variation that is inherited and affects all cells in the body, not just the leukemic cells.”

Relling’s team analyzed genetic variations in 487 children with ALL searching for evidence of the disease persisting after treatment and found 102 inherited variations called single-nucleotide polymorphisms (SNPs) associated with small amounts of enduring disease. Relling said, “A high proportion of the gene variations were related to levels of the chemotherapy in blood and in leukemia cells. Some were related to leukemia cell biology.”

The research team also found that 21 of these variations were associated with relapse, and an equal amount was linked to early response to treatment. In addition, the findings showed that a cluster of variations around a gene called IL15 that produces a protein called interleukin 15, causes leukemia cells to multiply. Prior studies have suggested that IL15 shields tumors from chemotherapy drugs. According to Relling, drugs that thwart the activity of this gene might help some patients respond better to treatment.

Overall results revealed that a total of 61.7 percent of the SNPs were associated with early response, relapse risk or the performance of antileukemic drugs. Relling stated, “Some of the gene variation is likely to cause differences among patients in how quickly their bodies rid themselves of the chemotherapy, and some of the variations are likely to penetrate through to the leukemia cells and have an influence on the inherent sensitivity of the leukemia cells to chemotherapy.”

Relling said the findings suggest that whole-body exposure to medications is really important to curing leukemia, which sends a different message to the cancer community. In addition, genes children inherit from their parents may affect the type of leukemia they develop.