Suppression der Expression von CDX4 (siehe Eintrag)
ohne Gefährdungspotential
Transduction of primary murine bone marrow cells with Cdx4 conferred serial replating activity in the absence of stroma, a surrogate assay for transformation/self-renewal potential. In control experiments, nontransduced cells did not replate. Bone marrow cells derived from 5-fluorouracil-treated BALB/c mice were transduced with MSCV-Cdx4-IRES-GFP and injected intravenously into lethally irradiated syngeneic recipient mice, and the transplanted mice were observed for disease development. Half of the transplant recipients developed acute myeloid leukemia, with a median latency of ≈300 days posttransplantation. The leukemia generated was transplantable to secondary recipients resulting in a similar phenotype 6–8 weeks after transplantation. In another study all mice transplanted with Cdx4-transduced bone marrow hematopoetic stem and progenitors cells succumbed to transplantable acute erythroleukemia, a rare subtype of acute myeloid leukemia, with a median latency of 309 days posttransplantation. Sequencing of retroviral integration sites in the Cdx4 leukemic mice did not identify recurrent integrations into genes listed in the Retrovirus Integration Database, indicating no major role of retroviral insertional mutagenesis in the development of the erythroid leukemias.
Thoene S et al., Blood Adv. 2019;3(22):3729-3739.
Bansal D et al., Proc Natl Acad Sci U S A. 2006;103(45):16924-16929.
