| First Author | Perkins AC | Year | 1993 |
| Journal | EMBO J | Volume | 12 |
| Issue | 10 | Pages | 3835-46 |
| PubMed ID | 8104786 | Mgi Jnum | J:14755 |
| Mgi Id | MGI:62917 | Doi | 10.1002/j.1460-2075.1993.tb06062.x |
| Citation | Perkins AC, et al. (1993) Conditional immortalization of mouse myelomonocytic, megakaryocytic and mast cell progenitors by the Hox-2.4 homeobox gene. EMBO J 12(10):3835-46 |
| abstractText | The murine myelomonocytic cell line WEHI-3B exhibits ectopic expression of the genes encoding the homeobox protein, Hox-2.4, and the myeloid growth factor, interleukin-3 (IL-3). We showed previously that concomitant expression of IL-3 and Hox-2.4 in bone marrow cells induced the development of transplantable growth factor-independent tumours resembling the WEHI-3B tumour. We have now investigated the effect of enforced expression of Hox-2.4 alone. Bone marrow cells were infected with Hox-2.4 retrovirus and then either cultured in agar or transplanted into irradiated mice. In vitro, colonies derived from virus-infected cells readily yielded IL-3-dependent, non-tumorigenic cell lines of the myelomonocytic, megakaryocytic and mast cell lineages. Surprisingly, both the establishment and maintenance of these lines required very high concentrations of IL-3 and reduced levels promoted differentiation. Transplanted mice analysed after 3 months appeared normal but their spleen and bone marrow contained abundant provirus-bearing progenitor cells, from which IL-3-dependent long-term cell lines could readily be established in vitro. Four of 18 animals monitored for up to 12 months eventually developed clonal leukaemia, associated in three cases with IL-3 production. Thus ectopic expression of Hox-2.4 enhances self-renewal of immature myeloid progenitors and progression to a fully malignant state is favoured by somatic mutations conferring autocrine production of IL-3. |
