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More than 100 small genetic variations affect a child's response to treatment for the most common type of childhood cancer, a finding that might lead to better treatments, U.S. researchers have said.
Acute lymphoblastic leukemia, or ALL, is a cancer of the blood and bone marrow. About 80% of children survive ALL, but they differ widely in their responses to treatment.
While most studies have looked at genetic mutations acquired by leukemia cells, researchers at St. Jude Children's Research Hospital in Tennessee and colleagues looked for inherited genetic variations that affect all cells in the body.
They searched 476 796 inherited variations, called single-nucleotide polymorphisms, or SNPs, that influence the number of cancer cells left over after the first course of chemotherapy, a marker known as minimal residual disease.
Samples were taken from two independent groups of children with newly diagnosed ALL. The study turned up 102 inherited genetic variations that appeared to be involved in response to leukemia treatment.
"We took those 102 and we tested whether they were involved in other related characteristics," Mary Relling of St. Jude, whose study appears in the Journal of the American Medical Association, said in a telephone interview.
They found 21 of these variations were associated with relapse, and another 21 were linked with a strong, early response to treatment.
They also found a cluster of variations around a gene called IL15, which makes a protein called interleukin 15 that causes leukemia cells to multiply. Other studies have suggested IL15 protects tumors from chemotherapy drugs.
Relling said drugs that knock out the activity of this gene could help some patients do better.
"It has been shown to have an effect on the ability of blood cells to die in response to chemotherapy, but it wasn't anybody's top candidate gene before," she said.
Relling said this might suggest that genes children inherited from their parents might affect the type of leukemia they develop.
Jun Yang of St. Jude said in a statement the findings show the importance of looking for genetic variations across the whole human genome, because many of these differences can affect a patient's response to treatment.
"Such information might help clinicians use drugs more effectively to overcome the patient's own genetic variation and reduce the chance of treatment failure," Yang said.
Acute lymphoblastic leukemia, or ALL, is a cancer of the blood and bone marrow. About 80% of children survive ALL, but they differ widely in their responses to treatment.
While most studies have looked at genetic mutations acquired by leukemia cells, researchers at St. Jude Children's Research Hospital in Tennessee and colleagues looked for inherited genetic variations that affect all cells in the body.
They searched 476 796 inherited variations, called single-nucleotide polymorphisms, or SNPs, that influence the number of cancer cells left over after the first course of chemotherapy, a marker known as minimal residual disease.
Samples were taken from two independent groups of children with newly diagnosed ALL. The study turned up 102 inherited genetic variations that appeared to be involved in response to leukemia treatment.
"We took those 102 and we tested whether they were involved in other related characteristics," Mary Relling of St. Jude, whose study appears in the Journal of the American Medical Association, said in a telephone interview.
They found 21 of these variations were associated with relapse, and another 21 were linked with a strong, early response to treatment.
They also found a cluster of variations around a gene called IL15, which makes a protein called interleukin 15 that causes leukemia cells to multiply. Other studies have suggested IL15 protects tumors from chemotherapy drugs.
Relling said drugs that knock out the activity of this gene could help some patients do better.
"It has been shown to have an effect on the ability of blood cells to die in response to chemotherapy, but it wasn't anybody's top candidate gene before," she said.
Relling said this might suggest that genes children inherited from their parents might affect the type of leukemia they develop.
Jun Yang of St. Jude said in a statement the findings show the importance of looking for genetic variations across the whole human genome, because many of these differences can affect a patient's response to treatment.
"Such information might help clinicians use drugs more effectively to overcome the patient's own genetic variation and reduce the chance of treatment failure," Yang said.
