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JCI table of contents: March 20, 2008

d whether other genes that are candidates for gene therapy approaches might pose a similar risk. A new study, carried out by Hans-Peter Kiem and colleagues, at the Fred Hutchinson Cancer Research Center, Seattle, has now indicated that early precursors of immune cells that had the gene HOXB4 delivered into them by a gammaretroviral vector became leukemic in 2 of 2 dogs and 1 of 2 macaques. In vitro analysis established a clear link between HOXB4 expression and leukemia, leading the authors to conclude that the use of HOXB4-based gene therapy would probably carry a high risk of leukemia and that extreme caution is needed when considering gene therapy approaches. The need for caution is echoed in an accompany commentary by Andre Larochelle and Cynthia E. Dunbar, at the National Institutes of Health, Bethesda, who discuss how important large animal studies, such as those reported by Hans-Peter Kiem and colleagues, are to minimize the risk of adverse events in humans receiving gene therapy in the future.

TITLE: High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector

Hans-Peter Kiem
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Phone: (206) 667-4425; Fax: (206) 667-6124; E-mail:

View the PDF of this article at:


TITLE: HOXB4 and retroviral vectors: adding fuel to the fire

Cynthia E. Dunbar
National Institutes of Health, Bethesda, Maryland, USA.
Phone: (301) 496-1434; Fax: (301) 496-8396; E-mail:

View the PDF of this article at:'/>"/>

Contact: Karen Honey
Journal of Clinical Investigation

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