Espanõl

Print Article
Email Article

Share

Cancer Resources > Cancer News > 2002 > April

Retroviral gene marker leads to murine leukemia in gene therapy experiment

Karla Gale

Last Updated: 2002-04-19 13:28:54 EDT (Reuters Health)

NEW YORK (Reuters Health) - In a rare sequence of events, gene transfer using a retroviral vector and an inert gene marker interacted to cause leukemia in mice, German investigators report.

"This does not mean that gene therapy is dangerous," Dr. Christopher Baum, of Hannover Medical School, told Reuters Health. "For one thing, it is more difficult to transform human cells to a cancerous state than it is for mouse cells. This just means we have to take a closer look at possible side effects related to gene therapy."

Dr. Baum and associates discuss in the April 19th issue of Science their toxicity study of a clinically useful marker gene introduced into murine bone marrow using a replication-defective retrovirus. The investigators expected to see no more than mild alterations in hematopoiesis, Dr. Baum noted. In the first five mice treated, no alterations turned up during 28 weeks after treatment.

However, when bone marrow cells from the mice were transplanted into 10 irradiated mice, hematopoietic disorders, including extramedullary hematopoiesis, preleukemia, and overt acute myeloid leukemia (AML) were observed by 22 weeks. Eight tertiary recipients developed lethal AML.

Repeating the experiments with other marker proteins yielded negative results. The researchers ruled out transgene sequence alterations, replication by the retroviruses, or activation of endogenous retroviral sequences as a cause for their findings.

They found that the vector-inserted gene integrated into the murine gene and activated an oncogenic transcription factor, which on its own would be insufficient to cause severe side effects, Dr. Baum noted. But combined with the gene marker, which was derived from a low-affinity, pro-apoptotic receptor for neurotrophins, leukemia was promoted.

"We think we need a dialectic approach to look into side effects and study worst-case scenarios. Then we can derive exact numbers of how big the risks will be when clinical trials are designed," Dr. Baum said.

Referring to this week's report of successful gene therapy for the treatment of severe combined immunodeficiency disorder (see Reuters Health report, April 17, 2002), he added, "You have to consider the risk-benefit ratio. These poor children don't have many choices, and it's currently the best treatment that can be offered to them. I would see no reason to stop such trials."

Science 2002;296:497.

Copyright © 2010 Reuters Limited. All rights reserved.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.