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

ABSTRACT: Retroviral vector-mediated HSC gene therapy has been used to treat individuals with a number of life-threatening diseases. However, some patients with SCID-X1 developed retroviral vector-mediated leukemia after treatment. The selective growth advantage of gene-modified cells in patients with SCID-X1 suggests that the transgene may have played a role in leukemogenesis. Here we report that 2 of 2 dogs and 1 of 2 macaques developed myeloid leukemia approximately 2 years after being transplanted with cells that overexpressed homeobox B4 (HOXB4) and cells transduced with a control gammaretroviral vector that did not express HOXB4. The leukemic cells had dysregulated expression of oncogenes, a block in myeloid differentiation, and overexpression of HOXB4. HOXB4 knockdown restored differentiation

SUBMITTER: Zhang XB 

PROVIDER: S-EPMC2268879 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature