Homeobox gene expression plus autocrine growth factor production elicits myeloid leukemia.
In the murine myelomonocytic leukemia WEHI-3B, proviral insertions have induced expression of the Hox-2.4 homeobox gene and the gene for the myeloid growth factor interleukin 3 (IL-3). To assess their potential oncogenic role, normal bone marrow cells were infected with retroviruses bearing the genes for IL-3 or IL-3 plus Hox-2.4. Unlike the IL-3 virus, the IL-3/Hox-2.4 virus was highly leukemogenic. Infected cells expressing both genes exhibited retarded differentiation in vitro, generated myelomonocytic cell lines, and provoked a rapid, transplantable myeloid leukemia in vivo. The oncogenic action of Hox-2.4 appears to derive from its ability to impede the IL-3-driven terminal differentiation of myeloid cells. The results suggest that homeobox genes can regulate key differentiation processes such as self-renewal capacity and that their inappropriate expression can be oncogenic.
Perkins
A
A
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Kongsuwan
K
K
Visvader
J
J
Adams
J M
JM
Cory
S
S
D000818:Animals; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D015342:DNA Probes; D015870:Gene Expression; D005801:Genes, Homeobox; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000235:genetics*; D007438:Introns; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D008811:Mice, Inbred DBA; D012190:Retroviridae / Q000235:genetics*
D015342:DNA Probes; D007377:Interleukin-3