HOXB4 and retroviral vectors: adding fuel to the fire.
The transcription factor homeobox B4 (HOXB4) is a promising agent capable of providing a growth advantage to genetically modified hematopoietic stem and progenitor cells (HSPCs). In this issue of the JCI, Zhang and colleagues overexpressed HOXB4 in HSPCs from large animals using retroviral vectors (see the related article beginning on page 1502). Two years after transplantation, most animals developed leukemia, a consequence of combined HOXB4 and deregulated protooncogene expression. These results highlight the risks of combining integrating vectors and growth-promoting genes for clinical applications.
Larochelle
Andre
A
Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dunbar
Cynthia E
CE
D000818:Animals; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012190:Retroviridae / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; D014157:Transcription Factors