Two children who developed leukemia after receiving gene therapy for an inherited disease may have been victims of a rare combination of genes that is unlikely to happen in gene therapy for other disorders, a study says.
Researchers at the National Cancer Institute in Frederick, Md., discovered that a gene in a virus used to treat the children, who had an inherited immune system disorder, can combine with another gene to cause leukemia in mice.
Dr. Utpal P. Dave, first author of a study appearing this week in the journal Science, said that he and his team found that in mice a gene called Lmo2 can combine with another gene, called IL2RG, to cause leukemia.
Ten children in France who suffered from severe combined immune deficiency, or SCIDS, were treated with a gene therapy that used a virus to transfer the IL2RG gene to their bone marrow.
This gene can correct SCIDS, causing the bone marrow to make normal immune system cells. The therapy worked against SCIDS in the children, but two of them developed leukemia, which was blamed on the gene therapy.
As a precaution, the Food and Drug Administration in January last year suspended 27 gene therapy trials in the United States.
Dave said the study by his team showed that the leukemia was caused by a rare combination of genes. This means that other forms of gene therapy would not face the same risk, he said.
He also said that by studying cancer-causing gene combinations in mice, researchers may be able to identify those that would cause cancer in humans.
"The mouse can serve as a tool to identify genes that cause leukemia, for instance,'' he said.
Dr. Phil Nouguchi of the FDA said the work of Dave and his team is important in helping to advance gene therapy as a valuable medical tool. But he said that even though the authors showed that the leukemia in the children was a rare event, each proposed gene therapy treatment needs to be examined "on a case by case basis.''
Nouguchi said some of the 27 gene therapy trials suspended last year have resumed, but that the FDA is still being cautious about tests of gene therapy techniques.